tbuckley/cabot-search huggingface dataset:
Abstract A61: Hexim-1 protein expression levels modulate TGFβ activity in prostate cancer
Authors: Manya Dhar-Mascareno, Eduardo Mascareno, Fang Liu
Journal: Cancer Research (2012)

Abstract Hexim-1 is a highly conserved protein from human to mouse, and a well-established inhibitor of RNA polymerase II-dependent transcription elongation and cell proliferation. Others and we have proposed and provided evidence that changes in the expression and activity in Hexim-1 significantly influence the progression of cancer. Here we show that changes in expression levels of Hexim-1 modulate TGFβ1 signaling by inducing posttranslational modifications in the SMADs proteins (small mother against decapentaplegic) at the polylinker region of the Smad1 and Smad3 proteins. Cdk9 serine activity not only targets specific serine residues in the carboxyl terminus of RNA polymerase II during transcriptional elongation but also serine residues in the polylinker region of Smad3. Hexim-1 directly inhibits Cdk9 activity, and therefore, transcription elongation and TGFβ1/Smad3 activity. Our results indicate that prostate cancer accompanies significant changes in Hexim-1 expression as well as sub cellular redistribution. Similar observations were obtained in the TRAMP mouse model of prostate cancer. In order to understand the role of Hexim-1 during prostate cancer progression, we generated a TRAMP mouse model heterozygous for Hexim-1. Our studies in the TRAMP mouse model revealed that lowered levels in Hexim-1 protein expression triggered a more aggressive form of prostate cancer. TGFβ1/Smad3 plays a significant role during proliferation, cell migration, as well as in epithelial mesenchymal transition, which is critical during metastasis. To test the role of Hexim-1 as a modulator of TGF/Smad3 in vitro, we use the epithelial mouse prostate cancer cell line TRAMP-C2 and derived the TRAMP-C2 heterozygous for Hexim-1 (HT). We observed increased serine 208 phosphorylation of Smad3 as well as enhanced transcriptional activity of TGF β/Smad3 target genes involved in EMT such as SM22alpha and alpha smooth muscle actin in the HT-TRAMP-C2 cell line. These findings suggest that Hexim-1 is a critical regulator of prostate cancer progression. Citation Format: Manya Dhar-Mascareno, Eduardo Mascareno, Fang Liu. Hexim-1 protein expression levels modulate TGFβ activity in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A61.
Role and species-specific expression of colon T cell homing receptor GPR15 in colitis
Authors: Linh P Nguyen, Junliang Pan, Thanh Theresa Dinh, Husein Hadeiba, Edward O'Hara, Ahmad Ebtikar, Arnulf Hertweck, M Refik Gökmen, Graham M Lord, Richard G Jenner, Eugene C Butcher, Aida Habtezion
Journal: Nature Immunology (2014)
How many medical students?
Authors: T D Brogan
Journal: BMJ (1977)

The recently introduced SPECT/CT integrates the physiologic data of SPECT with the anatomic data of CT into a single image. The purpose of this pilot study was to explore the additional value of SPECT/CT in breast cancer patients and melanoma patients with inconclusive planar image findings. <b>Methods:</b> Thirty-one patients had planar lymphoscintigrams showing unexpected lymphatic drainage, 6 had lymphoscintigrams that were difficult to interpret, and 3 showed no drainage on planar imaging. SPECT/CT was performed immediately after delayed planar imaging. <b>Results:</b> In 4 patients, SPECT/CT showed 6 additional sentinel nodes, of which 2 were tumor-positive and led to upstaging and tailored management in 5% of patients. SPECT/CT depicted sentinel nodes in 3 patients whose delayed planar imaging had shown no drainage. <b>Conclusion:</b> SPECT/CT was of additional value in finding the exact anatomic location of sentinel nodes in patients with inconclusive planar image findings. SPECT/CT also detected sentinel nodes in addition to those found on planar images, and SPECT/CT detected sentinel nodes in patients whose planar images had shown none.
Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase
Authors: J Cortes, D-W Kim, E Raffoux, G Martinelli, E Ritchie, L Roy, S Coutre, S Corm, N Hamerschlak, J-L Tang, A Hochhaus, H J Khoury, T H Brümmendorf, M Michallet, G Rege-Cambrin, C Gambacorti-Passerini, J P Radich, T Ernst, C Zhu, J M A Van Tornout, M Talpaz
Journal: Leukemia (2008)
Selection of medical treatment in stable angina pectoris: Results of the International Multicenter Angina Exercise (IMAGE) study
Authors: Diego Ardissino, Stefano Savonitto, Kenneth Egstrup, Klaus Rasmussen, Erling A. Bae, Tor Omland, Per M. Schjelderup-Mathiesen, Paolo Marraccini, Piera Angelica Merlini, Inger Wahlqvist, Nina Rehnqvist
Journal: Journal of the American College of Cardiology (1995)
Primary care for refugees and asylum seekers
Authors: Sally A Hull, Kambiz Boomla
Journal: BMJ (2006)

histologically confirmed precancer, women with abnormal cytology and HPV16 infection are at very high absolute risk of having a missed, small precancerous lesion (cervical intraepithelial neoplasia grade 3). 10 After excisional or ablative treatments of the cervix for precancer, the absolute risk of recurrence is about 5-10%.Testing for HPV four to six months after treatment is highly sensitive and specific for the risk of recurrence and is better than cytology alone for monitoring cure. 11 Regardless of their promise, switching to prevention strategies based on HPV testing warrants caution.Only one test has had extensive clinical validation.Before widespread adoption, all new HPV tests will require robust, real life evidence of reliability and accuracy in detecting precancer and cancer; otherwise, testing errors could mislead clinical management. 12Furthermore, even the low cost HPV tests now being developed will have to be used in targeted populations if they are to be cost effective.Excessive or misguided use will increase costs without adding benefit.Like most revolutionary technologies, HPV testing must be managed wisely to do good rather than harm.
Intraneuronal Aβ detection in 5xFAD mice by a new Aβ-specific antibody
Authors: Katherine L Youmans, Leon M Tai, Takahisa Kanekiyo, W Blaine Stine Jr, Sara-Claude Michon, Evelyn Nwabuisi-Heath, Arlene M Manelli, Yifan Fu, Sean Riordan, William A Eimer, Lester Binder, Guojun Bu, Chunjiang Yu, Dean M Hartley, Mary Jo LaDu
Journal: Molecular Neurodegeneration (2012)

Abstract Background The form(s) of amyloid-β peptide (Aβ) associated with the pathology characteristic of Alzheimer's disease (AD) remains unclear. In particular, the neurotoxicity of intraneuronal Aβ accumulation is an issue of considerable controversy; even the existence of Aβ deposits within neurons has recently been challenged by Winton and co-workers. These authors purport that it is actually intraneuronal APP that is being detected by antibodies thought to be specific for Aβ. To further address this issue, an anti-Aβ antibody was developed (MOAB-2) that specifically detects Aβ, but not APP. This antibody allows for the further evaluation of the early accumulation of intraneuronal Aβ in transgenic mice with increased levels of human Aβ in 5xFAD and 3xTg mice. Results MOAB-2 (mouse IgG 2b ) is a pan-specific, high-titer antibody to Aβ residues 1-4 as demonstrated by biochemical and immunohistochemical analyses (IHC), particularly compared to 6E10 (a commonly used commercial antibody to Aβ residues 3-8). MOAB-2 did not detect APP or APP-CTFs in cell culture media/lysates (HEK-APP Swe or HEK-APP Swe /BACE1) or in brain homogenates from transgenic mice expressing 5 familial AD (FAD) mutation (5xFAD mice). Using IHC on 5xFAD brain tissue, MOAB-2 immunoreactivity co-localized with C-terminal antibodies specific for Aβ40 and Aβ42. MOAB-2 did not co-localize with either N- or C-terminal antibodies to APP. In addition, no MOAB-2-immunreactivity was observed in the brains of 5xFAD/BACE -/- mice, although significant amounts of APP were detected by N- and C-terminal antibodies to APP, as well as by 6E10. In both 5xFAD and 3xTg mouse brain tissue, MOAB-2 co-localized with cathepsin-D, a marker for acidic organelles, further evidence for intraneuronal Aβ, distinct from Aβ associated with the cell membrane. MOAB-2 demonstrated strong intraneuronal and extra-cellular immunoreactivity in 5xFAD and 3xTg mouse brain tissues. Conclusions Both intraneuronal Aβ accumulation and extracellular Aβ deposition was demonstrated in 5xFAD mice and 3xTg mice with MOAB-2, an antibody that will help differentiate intracellular Aβ from APP. However, further investigation is required to determine whether a molecular mechanism links the presence of intraneuronal Aβ with neurotoxicity. As well, understanding the relevance of these observations to human AD patients is critical.
WARFARIN FOR PREVENTION OF THROMBOEMBOLISM IN ATRIAL FIBRILLATION: COMPARISON OF PATIENT CHARACTERISTICS AND OUTCOMES OF THE “REAL-WORLD” MICHIGAN ANTICOAGULATION QUALITY IMPROVEMENT INITIATIVE (MAQI2) REGISTRY TO THE RE-LY, ROCKET-AF, AND ARISTOTLE TRIALS
Authors: Andrew Hughey, Geoffrey Barnes, Xiaokui Gu, Brian Haymart, Eva Kline-Rogers, Steven Almany, Jay Kozlowski, Dennis Besley, Gregory D. Krol, Syed Ahsan, Scott Kaatz, James Froehlich
Journal: Journal of the American College of Cardiology (2014)
Medical folklore—the use of your stethoscope's bell
Authors: Michael Reschen
Journal: BMJ (2007)

In my efforts to tease out medicine's innermost secrets and succeed at the final hurdle to becoming a member of the Royal College of Physicians by passing the clinical examination (PACES), I have uncovered what I consider to be an interesting and neglected fact about the bell and diaphragm of most stethoscopes. 

Like a migrating bird, I return each Christmas to my birthplace, and more importantly to my parents' address, and set aside a few minutes to sort through my obsolete but emotive adolescent belongings. Rummaging around, I unearthed my Littman stethoscope's box, …
CCR5 Deficiency Exacerbates T-Cell–Mediated Hepatitis in Mice *
Authors: Christophe Moreno, Thierry Gustot, Charles Nicaise, Eric Quertinmont, Nathalie Nagy, Marc Parmentier, Olivier Le Moine, Jacques Devière, Hubert Louis
Journal: Hepatology (2005)

Abstract Experimental T-cell–mediated hepatitis induced by concanavalin A (Con A) involves the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands (CCL3, CCL4, and CCL5) regulate leukocyte chemotaxis and activation, we investigated the role of CCR5 during Con A–induced liver injury. Serum levels of CCR5 ligands and their hepatic transcript levels were significantly increased after Con A injection, whereas CCR5+ liver mononuclear cells were recruited to the liver. CCR5-deficient (CCR5−/−) mice disclosed increased mortality and liver injury following Con A administration compared with wild-type mice. CCR5−/− mice also exhibited increased production of interleukin 4, tumor necrosis factor α, CCL3, CCL4, and CCL5, and a prominent liver mononuclear cell infiltrate, among which many cells were CCR1+. In vivo neutralization of CCR5 ligands in CCR5−/− mice afforded a protection against hepatitis only when CCL5 was neutralized. In conclusion , CCR5 deficiency exacerbates T-cell–mediated hepatitis, and leads to increased levels of CCR5 ligands and a more pronounced liver mononuclear infiltrate, suggesting that CCR5 expression can modulate severity of immunomediated liver injury. (Hepatology 2005;42:854–862.)
English surgeons may at last be about to become doctors: Anyone for bolting on the German system?
Authors: William S Monkhouse
Journal: BMJ (2005)

Right to die" Legal view of right to life and death could threaten philosophy of palliative careEditor-Grayling claims that the "right to life" means quite a rich life; withholding treatment with death as the result and giving treatment that causes death are indistinguishable; and death is the ultimate analgesic. 1 Grayling also implies that the double effect is widely abused.The EC Convention for the Protection of Human Rights and Fundamental Freedoms protects against intentional deprivation of life. 2 Quality of life is not mentioned, and terminating a life at a person's request is clearly not permitted."Right to life" is perhaps a "right not to be killed," in medicine, generally relating to survival and not assisted death.However, some interpret it as giving patients a right to cardiopulmonary resuscitation regardless of the clinical circumstances 3 ; extrapolation to all potential interventions at the life-death interface could have disastrous consequences for the medical profession.Patients obviously can wish for their life to be terminated without needing to explain why, and they arguably have a right to attempt suicide.However, a right to assisted dying equates to a right that somebody else will kill or help to kill them on request-very different from withholding treatment or the double effect.Withholding treatment relates to interventions unable to produce the desired benefit. 4 In palliative care withholding treatment does not directly cause death that arises from an irreversible and unsustainable pathological burden.And death without adequate analgesia is possibly the ultimate pain for everyone.Judicious use of analgesia is an essential part of good terminal care, and, in 15 years as a doctor, I have yet to see a death attributable to deliberate analgesic overdose by a doctor.Palliative care affirms life until the moment of death, regarding death from advanced incurable disease as a natural process. 5 It aims to relieve pain and other distressing symptoms, enhance remaining quality of life, and neither hasten nor postpone death.These human "death rights" should perhaps be protected by legislation.Ill-conceived legislative changes that take the right to life or the right to death beyond sensible limits or give certain doctors the right to kill on request could jeopardise palliative care.
AN INFLUENTIAL DOCTOR
Authors: A. Crowther
Journal: BMJ (1996)

The general practitioner who influenced my subsequent 25 years in practice, Jimmie, as he was always known, had worked hard through the difficult years of the 1930s, through the restrictions of the second world war, and had reached an honourable retirement age. After retiring for several years he had returned to help out in an emergency until new principals could be found, and I joined the practice as a locum. Jimmie was very much of the old school, brought up in an age when there were few …
Indian government shelves plans for mercy killing law
Authors: N. Choudhuri
Journal: BMJ (2013)

The Indian government has dropped plans for a bill that would have laid down clear procedures for withdrawing treatment and life support in the best interests of terminally ill patients.

The plans, contained in a draft bill prepared in 2006 by the Law Commission of India, called Medical Treatment to Terminally Ill Patients, would have removed the need for relatives to apply to the High Court to stop treatment and feeding.1 

The draft bill proposed procedures that should be followed in cases where patients could not consent, to ensure that decisions were made in patients’ best interests and that medical practitioners involved …
Statins and Musculoskeletal Conditions, Arthropathies, and Injuries
Authors: Ishak Mansi, Christopher R. Frei, Mary Jo Pugh, Una Makris, Eric M. Mortensen
Journal: JAMA Internal Medicine (2013)

Statin use may be associated with increased musculoskeletal adverse events, especially in physically active individuals.To determine whether statin use is associated with musculoskeletal conditions, including arthropathy and injury, in a military health care system.A retrospective cohort study with propensity score matching.San Antonio Military Multi-Market.Tricare Prime/Plus beneficiaries evaluated from October 1, 2003, to March 1, 2010.Statin use during fiscal year 2005. On the basis of medication fills, patients were divided into 2 groups: statin users (received a statin for at least 90 days) and nonusers (never received a statin throughout the study period).Using patients' baseline characteristics, we generated a propensity score that was used to match statin users and nonusers; odds ratios (ORs) were determined for each outcome measure. Secondary analyses determined adjusted ORs for all patients who met study criteria and a subgroup of patients with no comorbidities identified using the Charlson Comorbidity Index. Sensitivity analysis further determined adjusted ORs for a subgroup of patients with no musculoskeletal diseases at baseline and a subgroup of patients who continued statin therapy for 2 years or more. The occurrence of musculoskeletal conditions was determined using prespecified groups of International Classification of Diseases, Ninth Revision, ClinicalModification codes: Msk1, all musculoskeletal diseases; Msk1a, arthropathies and related diseases; Msk1b, injury-related diseases (dislocation, sprain, strain); and Msk2, drug-associated musculoskeletal pain.A total of 46 249 individuals met study criteria (13 626 statin users and 32 623 nonusers). Of these, we propensity score-matched 6967 statin users with 6967 nonusers. Among matched pairs, statin users had a higher OR for Msk1 (OR, 1.19; 95% CI, 1.08-1.30), Msk1b (1.13; 1.05-1.21), and Msk2 (1.09; 1.02-1.18); the OR for Msk1a was 1.07 (0.99-1.16; P = .07). Secondary and sensitivity analyses revealed higher adjusted ORs for statin users in all outcome groups.Musculoskeletal conditions, arthropathies, injuries, and pain are more common among statin users than among similar nonusers. The full spectrum of statins' musculoskeletal adverse events may not be fully explored, and further studies are warranted, especially in physically active individuals.
FURTHER STUDIES WITH TOXIC SERUM EXTRACTS OF HEMOLYTIC STREPTOCOCCI
Authors: Julia T. Weld
Journal: The Journal of Experimental Medicine (1935)

1. The same Streptococcus hemolyticus organisms may be subjected to extraction six times in 2 days with untreated inactivated serum with no loss in potency of the later extracts when the organisms are kept frozen solid during the night between the extractions. 2. The serum extract toxins of hemolytic streptococci can be preserved without deterioration for at least 6 months if kept frozen solid. 3. No toxins stronger than those containing 10 units per cc. for mice have been prepared. Reasons for thinking that this is due to the saturation of the serum with the toxin at this point are given. 4. Half saturation with (NH4)2SO4 precipitates out practically all of the hemotoxin in a preparation. 5. Serum extracts were made from strains of hemolytic streptococci other than the Gay strain and attempts were made to correlate the virulence and toxin production from each strain. No such correlation could be established. 6. The principal pathologic finding in mice inoculated with the streptococcus serum extract toxin is a marked degeneration of the tubular epithelium of the kidney.
Causes and Treatment of Postmastectomy Lymphedema of the Arm
Authors: Richard C. Britton
Journal: JAMA (1962)

Etiologic factors were sought in a study of 114 patients with lymphedema of the arm after radical mastectomy. In 94 of these there had not been any local recurrence of the cancer. The results suggested that infection was of primary importance. Radiodermatitis, late fibrosis in the axilla due to radiation or surgery, and anatomical or functional obstruction of the axillary vein were major contributing factors. Localized induration and barely perceptible warmth in the arm and forearm were consistent physical findings of chronic subclinical infection which disappeared with appropriate antibiotic treatment. Control of existing infection, instruction in skin care, restoration of shoulder function, pneumatic compression to eliminate pitting edema, and wearing of a precision-fitted elastic sheath were effective in controlling edema in about 90% of the patients.
A case report of Hailey–Hailey disease treated with alefacept (Amevive<sup>®</sup>)
Authors: D.S. Hurd, C. Johnston, A. Bevins
Journal: British Journal of Dermatology (2007)

Journal Article A case report of Hailey–Hailey disease treated with alefacept (Amevive®) Get access D.S. Hurd, D.S. Hurd Department of Dermatology, Edward Via Virginia College of Osteopathic Medicine, Blacksburg, VA, U.S.A. *Department of Dermatology, West Virginia University, Morgantown, WV, U.S.A. †Department of Internal Medicine, Norton Community Hospital, Norton, VA, U.S.A. Correspondence: Daniel S. Hurd. E‐mail: thehurdsx3@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar C. Johnston, C. Johnston Department of Dermatology, Edward Via Virginia College of Osteopathic Medicine, Blacksburg, VA, U.S.A. *Department of Dermatology, West Virginia University, Morgantown, WV, U.S.A. †Department of Internal Medicine, Norton Community Hospital, Norton, VA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar A. Bevins A. Bevins Department of Dermatology, Edward Via Virginia College of Osteopathic Medicine, Blacksburg, VA, U.S.A. *Department of Dermatology, West Virginia University, Morgantown, WV, U.S.A. †Department of Internal Medicine, Norton Community Hospital, Norton, VA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 2, 1 February 2008, Pages 399–401, https://doi.org/10.1111/j.1365-2133.2007.08248.x Published: 01 February 2008
The Selective Bacteriostatic Action of Gentian Violet
Authors: L. P. Garrod
Journal: BMJ (1942)

It was first shown by Churchman (1912) that gentian violet inhibits the growth of almost all Gram-positive bacteria in a concentration permitting the growth of most Gramnegative species.That susceptibility to this action varies remarkably even among closely related Gram-positive bacteria was shown by experiments of my own (Garrod, 1933) using several strains of each of six species of Gram- positive coccus, and media containing various concentra- tions of gentian violet, crystal violet, Hofmann violet, methyl violet, and dahlia.There was little to choose between these five dyes, and not much strain variation in resistance among the bacteria: a true picture of their behaviour could thus be obtained by averaging the whole of these results, which gave the following as the lowest concentrations completely preventing growth: Average Lowest Inhibitory Concentration In Broth In 5% Serum Broth Streptococcus faecalis ..
Catheter probe extraductal ultrasonography vs. conventional endoscopic ultrasonography for detection of bile duct stones
Authors: T. Wehrmann, K. Martchenko, A. Riphaus
Journal: Endoscopy (2009)

See also: Commentaire de travail de T. Wehrmann et al., pp. 133Endoscopy 2009; 41(02): 251-252DOI: 10.1055/s-0032-1306732
Patenting of genes moves one stage closer
Authors: R. Watson
Journal: BMJ (1997)

The prospect of legislation across the European Union protecting biotechnological inventions moved a stage closer last week when the scheme won overwhelming approval from the European parliament.

The support of MEPs for the draft legislation, which has been widely criticised by various environmental and religious groups, was in marked contrast to the stance they adopted two and a half years ago. Then, largely swayed by the moral issues involved, the parliament used new legislative powers to kill the proposal.

The latest version is designed to take on board some of those earlier fears by stipulating that “discoveries” of elements that already …