tbuckley/cabot-search huggingface dataset:
Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.
Authors: B Williams, P Tsai, R W Schrier
Journal: Journal of Clinical Investigation (1992)

Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface receptor Bmax but did not influence receptor Kd. This receptor downregulation was not reproduced by osmotic control media containing either L-glucose or mannitol. Receptor downregulation was maximal at a glucose concentration of 15-20 mM and required 24-48 h for a maximum effect. Normalization of the extracellular glucose concentration allowed complete recovery of AVP and AII binding within 48 h. Receptor downregulation was associated with depressed AVP and AII-stimulated intracellular signaling and cell contraction. High glucose concentrations induced a sustained activation of protein kinase C (PKC) in VSMC, which was prevented by coincubation with H-7. H-7 also markedly attenuated glucose-induced downregulation of AVP and AII receptors on VSMC. This study demonstrates a novel cellular mechanism whereby high extracellular glucose concentrations directly and independently downregulate pressor hormone receptors and their function on vascular tissue via glucose-stimulated PKC activation.
Anti-Ro(SSA) positive rheumatoid arthritis (RA): a clinicoserological group of patients with high incidence of D-penicillamine side effects.
Authors: H M Moutsopoulos, F N Skopouli, A K Sarras, C Tsampoulas, A K Mavridis, S H Constantopoulos, P J Maddison
Journal: Annals of the Rheumatic Diseases (1985)

The clinical, laboratory, histological, and radiological manifestations of 90 Greek patients with anti-Ro(SSA) negative rheumatoid arthritis (RA) were compared with those of 15 Greek patients with anti-Ro(SSA) positive RA. Anti-Ro(SSA) positive RA patients had the same articular and extra-articular manifestations as anti-Ro(SSA) negative patients. However, they were predominantly females with lower rheumatoid factor titres and a high incidence of positive minor salivary gland biopsy specimens for Sjögren's syndrome. Finally, anti-Ro(SSA) positive RA patients frequently experienced penicillamine side effects.
Measuring performance or balancing the budget
Authors: N. Tyre
Journal: BMJ (1987)

inner city multiracial environment we are familiar with the difficulties caused by hidden prejudices.Though prejudice towards women in medicine may come from within the medical profession, patients may also be reluctant to consult women doctors, giving rise to another, hidden, difficulty for women doctors.We examined this possibility in a survey of 100 consecutive patients attending a rheumatology outpatient clinic in Hackney.We used a structured questionnaire to determine whether patients wanted to see male/female, old/young, or senior/ junior doctors.for their rheumatology consultation.The table summarises the results.Type of doctor preferred by 100 patients attending a rheumatology clinic Characteristics ofdoctor Preferences
Embryonic stem cells and tissue engineering: delivering stem cells to the clinic
Authors: A Vats, N S Tolley, A E Bishop, J M Polak
Journal: Journal of the Royal Society of Medicine (2005)

One of the challenges facing biomedical science is of its own making—namely, the progressive increase in lifespans. An increasing number of individuals require treatment and the treatments themselves have to work for longer. A shift in emphasis is therefore required towards biological approaches including the regeneration of tissues. Tissue engineering can be best defined by its goal—the design and construction in the laboratory of living components that can be used for the maintenance, repair or replacement of malfunctioning tissues. In this discipline, born in 1933 when tumour cells were wrapped in a polymer membrane and implanted into a pig,1 the life sciences and medicine come together with engineering in activities centred on three basic components—cells, scaffolds and signals. The development of tissue engineering has lately been spurred by the increased availability of cell sources, proteomics, the advent of new biomaterials, improvements in bioreactor design and increased understanding of healing. However, neither commercial development nor clinical application of tissue engineered products has kept pace with this rapidly evolving research. Industrial development has been hindered by difficulties in devising cost-efficient processes, guaranteeing product viability and satisfying the regulators. Nevertheless, the coming years will see a large increase in the number of patients benefiting from tissue engineering. For the cell biology component of tissue engineering, the greatest challenge is to optimize the isolation, proliferation and differentiation of cells and to design scaffolds or delivery systems that yield tissue growth in three dimensions. Ideally, we would harvest stem cells from a patient, expand them in cell culture, seed them on a scaffold and then implant the resultant tissue. Stem cells, when given the specific biological stimuli, can differentiate to become many types of specific mature cells, and use of these cells avoids the immunorejection that can occur with donor transplants. In addition, the technique of somatic nuclear transfer allows the creation of autologous cells and tissues from allogeneic embryonic stem cells. It is then important for the scaffold to act as a template and stimulus for proliferation and differentiation of the stem cells into the mature cells that will generate specific new tissue. The tissue can be grown on a scaffold that will resorb, so that only the new tissue will be implanted, or a 'biocomposite' of the scaffold and new tissue can be implanted. After implantation, the tissue-engineered construct must be able to survive, restore normal function and integrate with the surrounding tissues.
Preserved Outer Retina in AIPL1 Leber's Congenital Amaurosis: Implications for Gene Therapy
Authors: Jonathan Aboshiha, Adam M. Dubis, Jacqueline van der Spuy, Koji M. Nishiguchi, Edward W. Cheeseman, Carmen Ayuso, Miriam Ehrenberg, Francesca Simonelli, James W. Bainbridge, Michel Michaelides
Journal: Ophthalmology (2015)
Surgical Capsule of the Benign Enlargement of the Prostate
Authors: J. E. Semple
Journal: BMJ (1963)

<h3>Abstract</h3> Breast, lung, and colorectal cancer resistance to molecular targeted therapy is a major challenge and unfavorably impacts clinical outcomes, leading to hundreds of thousands of deaths yearly. In ERBB2+ cancers regardless of the tissue of origin, ERBB2 is the driver oncogene of resistance. We discovered that the ERBB2+ cancers are enriched with poly U sequences on their 3’UTR AU rich elements which are mRNA stabilizing sequences. We developed a novel technology, in which we engineered these ERBB2 mRNA stabilizing sequences to unstable forms and specifically controlled and degraded ERBB2 transcript and protein across multiple cancer types both in the wildtype and drug resistance settings <i>in vitro</i> and <i>in vivo</i>, offering a unique novel modality to control ERBB2 and other pervasive oncogenic signals where other therapies fail. <h3>One-Sentence Summary</h3> Engineered destabilized 3’UTR ARE of ERBB2 degrades ERBB2 in many cancer types and controlled resistance. <h3>Graphical abstract</h3>
Impartial careers advice for doctors and medical students
Authors: R. MacDonald
Journal: BMJ (2003)

Research published this week by BMJ Careers adds to the growing evidence of what we intuitively knew already: the majority of medical students and doctors in training are dissatisfied with the careers advice and guidance they receive. Informing Choices: the need for career advice in medical training reports on the views and experiences of 1740 doctors and medical students working in England (see further information box for more details).

Other studies, such as the BMA cohort study that reports on career paths and experiences of doctors who graduated in 1995, confirm that this dissatisfaction is a United Kingdom wide phenomenon.1

As one of the authors of Informing Choices , Charles Jackson, said in an interview in this week's Career Focus (p s191): “We weren't surprised to …
Abstract 1124: Site-specific DICER and DROSHA RNA products control the DNA-damage response.
Authors: Fabrizio d'Adda di Fagagna
Journal: Cancer Research (2013)

Abstract The DNA damage response (DDR) is a signaling pathway that arrests the proliferation of cells undergoing genotoxic events to preserve genome stability and as such plays important tumor suppressing functions. DICER and DROSHA are crucial ribonucleases involved in RNA interference (RNAi). Components of RNAi are thought to have evolved to preserve genome stability from the attacks of viruses and mobile genetic elements. RNA products generated by DICER and DROSHA are involved in chromatin assembly, gene silencing and cancer. So far, RNAi and DDR pathways have not been demonstrated to directly interact. We have recently shown in human, mouse and zebrafish that DICER and DROSHA, but not downstream elements of the RNAi pathway, are necessary to activate the DDR upon exogenous DNA damage and oncogene-induced genotoxic stress, as studied by DDR foci formation and by checkpoint assays. Indeed, oncogene-induced senescent cells, upon DICER or DROSHA inactivation, escape DDR-imposed arrest and proliferate again. DDR foci are sensitive to RNase A treatment and DICER- and DROSHA-dependent RNA products are required to restore DDR foci in RNase-A-treated cells. Through RNA deep sequencing and the study of DDR activation at a single inducible DNA double-strand break, we demonstrate that DDR foci formation requires site-specific DICER- and DROSHA-dependent small RNAs, named DDRNAs, which act in a MRE11-RAD50-NBS1- complex-dependent manner to fuel DDR. DDRNAs, either chemically synthesized or in vitro generated by DICER cleavage, are sufficient to restore the DDR in RNase-A-treated cells, also in the absence of other cellular RNAs. We propose an unanticipated direct role of a novel class of ncRNAs in the control of DDR activation at sites of DNA damage. The relevance of these findings in the context of tumor suppression will be discussed. Citation Format: Fabrizio d'Adda di Fagagna. Site-specific DICER and DROSHA RNA products control the DNA-damage response. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1124. doi:10.1158/1538-7445.AM2013-1124
TCR-Ligand <i>k</i> <sub>off</sub> Rate Correlates with the Protective Capacity of Antigen-Specific CD8 <sup>+</sup> T Cells for Adoptive Transfer
Authors: Magdalena Nauerth, Bianca Weißbrich, Robert Knall, Tobias Franz, Georg Dössinger, Jeannette Bet, Paulina J. Paszkiewicz, Lukas Pfeifer, Mario Bunse, Wolfgang Uckert, Rafaela Holtappels, Dorothea Gillert-Marien, Michael Neuenhahn, Angela Krackhardt, Matthias J. Reddehase, Stanley R. Riddell, Dirk H. Busch
Journal: Science Translational Medicine (2013)

A Strep tamer-based k off rate assay identifies T cells with high protective capacity for the adoptive transfer.
Abstract B40: Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties
Authors: Mona Mostafa Mohamed, Eslam A. El-Ghonaimy, Mohamed A. Nouh, Robert J. Schneider, Bonnie F. Sloane, Mohamed El-Shinawi
Journal: Cancer Research (2013)

Abstract Introduction: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is characterized by rapid progression and dismal outcome. Although there is a growing literature describing the role of macrophages in non-IBC, the role of macrophages in IBC is unclear. The aims of the present study were to: 1) assess macrophages infiltration within the tumor tissues of non-IBC and IBC patients; 2) isolate and profile cytokines of macrophages drained from breast tumor axillary tributaries of non-IBC and IBC patients and 3) test whether major cytokines secreted by tumor draining macrophages induce motility of the IBC cell line SUM149. Methods: Tumor-infiltrating macrophages were measured by immunohistochemical (IHC) techniques using CD14 and CD68 monoclonal antibodies. Blood drained from axillary vein tributaries was collected from non-IBC and IBC patients during breast cancer surgery and total mononuclear cells isolated by density gradient centrifugation using Histopaque. The percentage of monocytes/macrophages (CD14+) in the total isolated leukocytes was calculated by flow cytometry using fluorochrome-labeled monoclonal antibodies (APC-CD14 and PerCP-CD3). CD14+ population was separated from total mononuclear cells using an immuno-magnetic bead separation technique. CD14+ cells were seeded overnight in appropriate culture media at 37°C in a humidified CO2 incubator and conditioned media were collected and cytokines profiled. To test whether cytokines secreted by CD14+ enhances motility and invasion of SUM149 cells, we used wound healing and invasion assays. Results: Our results revealed that there was an increase in the number of infiltrated macrophages (CD14+ cells) in IBC tumor tissues and axillary tributaries drained blood as compared to non-IBC. Cytokine profiling of IBC-CD14+ cells revealed a significant increase in tumor necrosis factor-alpha (TNF-α); monocyte chemoattractant protein-1 (MCP-1) also known as CC-chemokine ligand 2 (CCL-2); interleukin-10 (IL-10) and interleukin-8 (IL-8) as compared to non-IBC CD14+ cells. TNF-α, IL-8 and IL-10 cytokines significantly increased motility and invasion of SUM149 cells. Conclusion: IBC cancer tissues are characterized by high infiltration of monocytes/macrophages that secrete cytokines that may contribute to dissemination of IBC cells. Citation Format: Mona Mostafa Mohamed, Eslam A. El-Ghonaimy, Mohamed A. Nouh, Robert J. Schneider, Bonnie F. Sloane, Mohamed El-Shinawi. Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B40.
Relationship Between EGFR Expression, EGFR Mutation Status, and the Efficacy of Chemotherapy Plus Cetuximab in FLEX Study Patients with Advanced Non–Small-Cell Lung Cancer
Authors: Jean-Yves Douillard, Robert Pirker, Kenneth J. O’Byrne, Keith M. Kerr, Stephan Störkel, Anja von Heydebreck, Hans Jürgen Grote, Ilhan Celik, Frances A. Shepherd
Journal: Journal of Thoracic Oncology (2014)
Factitial vs Factitious
Authors: E. Fritz Schmerl
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Weinstein et al (233:878, 1975) reported an interesting study on what they call factitious meningitis. On a Gram stain of cerebrospinal fluid, they detected organisms that had been adventitiously introduced from specimen tubes and that proved nonviable. The authors warn that this can lead to an erroneous diagnosis of meningitis. The term "factitious meningitis" is, I submit, unfelicitous. The choice, it seems to me, should be<i>factitial</i>rather than factitious. Both of these terms imply human action, but there is a fine distinction:<i>factitious</i>denotes deliberation or intent, as in "factitious dermatitis";<i>factitial</i>, as in "factitial rectal lesions following irradiation" (<i>Webster's Third New International Dictionary</i>. Springfield, Mass, G &amp; C Merriam Co) does not assume intent and is, therefore, more accurate in Dr Weinstein's case. The difference is important not only as a matter of exactitude but, perhaps, in its medicolegal aspect. Ironically, this "blooper" appeared in
Intravenous Immune Globulin in the Therapy of Myocarditis and Acute Cardiomyopathy
Authors: Dennis M. McNamara, Warren D. Rosenblum, Karen M. Janosko, Mary K. Trost, Flordeliza S. Villaneuva, A.J. Demetris, Srinivas Murali, Arthur M. Feldman
Journal: Circulation (1997)

Although an autoimmune pathogenesis has been postulated for dilated cardiomyopathy, immunosuppressive therapy has not been shown to be effective in clinical trials. Immune modulatory therapy with immune globulin is an effective therapy for Kawasaki disease in children, and recent data suggest that it improves ventricular function in children with new-onset dilated cardiomyopathies. The role of immune globulin therapy in adults with this disorder has not previously been evaluated.Ten patients were treated with high-dose intravenous immune globulin infusions (2 g/kg). All were hospitalized with NYHA class III to IV heart failure, left ventricular ejection fraction (LVEF) < 0.40, and symptoms for < 6 months at the time of presentation. One patient died before the completion of therapy. The remaining 9 were discharged, and LVEF was reassessed 12 months after therapy. LVEF improved from 0.24 +/- 0.02 (mean +/- SEM) at baseline to 0.41 +/- 0.04 at follow-up (P = .003). All 9 patients improved functionally to NYHA class I to II, and there have been no subsequent hospitalizations for heart failure during the course of follow-up.In this series of patients with new-onset dilated cardiomyopathy treated with high-dose immune globulin, LVEF improved 17 EF units. The effectiveness of intravenous immune globulin therapy in this disorder should be evaluated in a randomized, multicenter trial.
Molecular analysis of hematopoietic colonies derived from chronic myeloid leukemia patients: interphase fluorescence in situ hybridization compared with RT-PCR
Authors: SFT Thijsen, GJ Schuurhuis, JW van Oostveen, AP Theijsmeijer, MMAC Langenhuijsen, GJ Ossenkoppele
Journal: Leukemia (1997)
INFLUENCE OF NON-UNIFORM STENT EXPANSION ON NEOINTIMAL HYPERPLASIA AFTER BARE-METAL AND ZOTAROLIMUS-ELUTING STENTS IMPLANTATION
Authors: Daisaku Nakatani, Katsuhisa Waseda, Hiromasa Otake, Junya Ako, Paul G. Yock, Peter J. Fitzgerald, Yasuhiro Honda
Journal: Journal of the American College of Cardiology (2010)
Second malignancies in Hodgkin's disease: a complication of certain forms of treatment.
Authors: P Valagussa, A Santoro, R Kenda, F Fossati Bellani, F Franchi, A Banfi, F Rilke, G Bonadonna
Journal: BMJ (1980)

A total of 764 patients with Hodgkin9s disease treated with radiotherapy (RT) or chemotherapy or both were reviewed 3-186 months (median 43 months) after initial treatment to assess the incidence of second malignancies. Incidence of solid tumours and acute non-lymphoblastic leukaemia (ANLL) were calculated by a life-table method and percentages of patients affected derived from life-table plots. Within 10 years after initial treatment the overall incidence of second solid tumours was 7.3%, and over a comparable period 2.4% of patients developed ANLL. Solid tumours occurred only in patients given RT with or without adjuvant chemotherapy, and ANLL occurred only after treatment with MOPP (mustine, vincristine, procarbazine, and prednisolone) or modified MOPP regimens. Neither solid tumours nor ANLL occurred in patients given ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The highest incidence of leukaemia (5.4%) occurred after treatment with extensive RT plus (5.4%) occurred after treatment with extensive RT plus MOPP; hence the benefits of this approach in Hodgkin9s disease must be weighed against its carcinogenic potential.
STUDIES IN THE ETIOLOGY OF BRONCHIAL ASTHMA
Authors: JOHN EIMAN
Journal: JAMA (1927)

In these studies I limited myself strictly to bronchial asthma, or the so-called idiopathic or essential bronchial asthma. Cases of asthma due to sensitization to animal proteins, excretions and secretions were excluded. Likewise, individuals sensitive to pollens, plant proteins and foodstuffs were eliminated. Most of the cases studied came from Dr. H. B. Wilmer's Asthma Clinic at the Presbyterian Hospital.  All these patients had chronic infections either of the bronchi or sinuses, or both, with varying amounts of mucopurulent secretions. Many of them were more comfortable and some were entirely free from asthma during the summer months, when their respiratory infections had subsided temporarily. With the onset of cold weather and the prevalence of upper respiratory infections, the asthmatic condition invariably became aggravated. This was always coincident with an increase in mucopurulent bronchial or nasal secretions. The relationship between the asthmatic attacks and the respiratory infections was unmistakable. Rosneau and
Amelioration of ischemia- and reperfusion-induced myocardial injury by the selective estrogen receptor modulator, raloxifene, in the canine heart
Authors: Hisakazu Ogita, Koichi Node, Hiroshi Asanuma, Shoji Sanada, Yulin Liao, Seiji Takashima, Masanori Asakura, Hidezo Mori, Yoshiro Shinozaki, Masatsugu Hori, Masafumi Kitakaze
Journal: Journal of the American College of Cardiology (2002)
Inflammasome-derived IL-1β production induces nitric oxide–mediated resistance to Leishmania
Authors: Djalma S Lima-Junior, Diego L Costa, Vanessa Carregaro, Larissa D Cunha, Alexandre L N Silva, Tiago W P Mineo, Fredy R S Gutierrez, Maria Bellio, Karina R Bortoluci, Richard A Flavell, Marcelo T Bozza, João S Silva, Dario S Zamboni
Journal: Nature Medicine (2013)
Myocardial Discontinuities
Authors: James B. White, Gregory P. Walcott, Andrew E. Pollard, Raymond E. Ideker
Journal: Circulation (1998)

Background —Theoretical models suggest that an electrical stimulus causes regions of depolarization and hyperpolarization on either side of a myocardial discontinuity. This study determined experimentally whether an artificial discontinuity gives rise to an activation front in response to an electrical stimulus, consistent with the creation of such polarized regions. Methods and Results —After a thoracotomy in six dogs, a 504-unipolar-electrode plaque was sutured to the right ventricular epicardium to map activations. From a line electrode parallel to one side of the plaque, 10 S 1 stimuli were delivered, followed by S 2 and S 3 stimuli (S 1 S 1 , S 1 S 2 , S 2 S 3 interval=300 ms). S 1 and S 3 stimuli were 25 mA; 5-ms S 2 stimuli of both polarities were initially 25 mA and increased in 25 mA increments. The plaque was removed, and a transmural incision was made through the ventricular wall in the middle of the mapped region and sutured closed. The plaque was replaced and the stimulation protocol repeated. Before the incision, S 2 stimuli directly activated tissue only near the stimulation site. An activation front arose at the border of the directly activated region and propagated across the plaque. As the S 2 stimulus strength was increased, the size of the directly activated region increased. After the incision, sufficiently large S 2 stimuli caused direct activation of tissue adjacent to the transmural incision as well as at the stimulation site. Activation fronts that arose adjacent to the transmural incision either propagated proximally toward the stimulation site and collided with the activation front originating from the stimulation wire or propagated distally away from the incision. Minimum S 2 stimulus strengths activating areas adjacent to the incision were only 45±14% (cathode) and 39±18% (anode) of the strengths required to directly activate the same area before the incision was formed ( P &lt;.05). Conclusions —Myocardial discontinuities can give rise to activation fronts after a stimulus, suggesting the presence of polarized regions adjacent to the discontinuity.
Detection of Paravascular Lamellar Holes and Other Paravascular Abnormalities by Optical Coherence Tomography in Eyes with High Myopia
Authors: Noriaki Shimada, Kyoko Ohno-Matsui, Akinobu Nishimuta, Muka Moriyama, Takeshi Yoshida, Takashi Tokoro, Manabu Mochizuki
Journal: Ophthalmology (2007)