tbuckley/cabot-search huggingface dataset:
Abstract 4136: Effects of magnolol on cell cycle, STAT 3, NF-kappa B and AKT signaling
Authors: Shivani Chilampalli, Radhey S. Kaushik, Gudiseva Chandrasekher, Hesham Fahmy, Chandradhar Dwivedi
Journal: Cancer Research (2010)

Abstract Magnolol is plant lignan isolated from bark and seed cones of Magnolia glaucan has been investigated for its anticancer effects. Previous studies from our laboratory have shown magnolol to be chemopreventive against UVB-caused skin carcinogenesis by inducing apoptosis. The objective of present study is to investigate other mechanisms involved for its chemopreventive effects. For this investigation, A431 human epidermoid carcinoma cells were used. Effects of magnolol on cell cycle were determined by flow cytometry. Expressions of various proteins involved in cell cycle were determined by Western blotting using appropriate antibodies. A431 human epidermoid carcinoma cells were incubated with different concentrations at different time periods. We further investigated the effects of magnolol on signal transducer and activator of transcription (STAT 3), nuclear factor-kappa B (NF-kappa B/p65) and AKT signaling pathways that play an important role in cell proliferation and survival. Magnolol at 100 μM and 125 µM caused G0/G1 cell cycle arrest by decreasing cyclin D1, cyclin D2, and CDK 4 and by increasing CDK inhibitors p21 and p27 at 24 and 48 h. We further found that magnolol inhibited expressions of STAT 3, NF-kappa B and AKT by inhibiting their phosphorylation at 24 and 48 h. These results indicate that chemopreventive effects of magnolol are mediated through multiple mechanisms. This study is supported by Translational Cancer Research Center funded as one of the 2010 Research Initiative Center by the State of South Dakota. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4136.
Trials of implantable monitoring devices in heart failure: which design is optimal?
Authors: William T. Abraham, Wendy G. Stough, Ileana L. Piña, Cecilia Linde, Jeffrey S. Borer, Gaetano M. De Ferrari, Roxana Mehran, Kenneth M. Stein, Alphons Vincent, Jay S. Yadav, Stefan D. Anker, Faiez Zannad
Journal: Nature Reviews Cardiology (2014)
Brain Development, II: Establishing Synaptic Connections
Authors: Carol A. Tamminga
Journal: American Journal of Psychiatry (1998)

Establishing Synaptic ConnectionsD uring normal CNS development, neurons in various brain regions express chemical markers that attract ingrowing neuronal terminals to form synapses with their correct targets.A single group of neurons within a neuronal structure may offer distinctive chemical cues that are organized into meaningful anatomic patterns to attract afferents from different brain regions.The cerebellum, for example, receives axons from spinal cord neurons whose terminals are distributed into distinct columns in the cerebellar cortex (bright pink areas in left figure).The terminals of spinocerebellar axons are labeled by injecting a dye, horseradish peroxidase, into the spinal cord, where it is taken up by neurons and transported to their terminal ends.The distinctive distribution of terminals in the cerebellum correlates with biochemical differences among cerebellar Purkinje cells.Thus, it is thought that the Purkinje cells express the chemical markers that organize the spinocerebellar terminals into distinct fields.This model is being tested by studying a genetic strain of mice, staggerer, that fails to develop mature Purkinje cells.Staggerer (gene symbol, sg) is an autosomal recessive mutation that causes a block in the development of cerebellar Purkinje cells.The number of Purkinje cells is reduced by 75%, and the surviving Purkinje cells fail to differentiate completely.As a consequence of this Purkinje cell loss, the vast majority of granule cells (primary afferents to Purkinje cells) in the cerebellar cortex also die.If Purkinje cells are the organizers for cerebellar afferent projections, then in their absence the organization of spinocerebellar afferents should be disrupted.In older staggerer mice, the terminals of spinocerebellar axons are indeed reduced in density and lack any apparent organization.However, in juvenile staggerer mice (right figure), the afferent terminals still can be seen to form a pattern that is approximately normal, even in a cerebellum diminished by granule and Purkinje cell loss.The results suggest that even immature Purkinje cells may express the chemical markers that allow afferent axons to sort out into distinct columns.Modern molecular techniques have identified a growing number of transcription factors (DNA binding proteins such as Engrailed and Pax), nerve cell adhesion molecules (e.g., N-CAM), and signaling molecules (e.g., the semiphorins and collapsins) with distinct expression patterns in the developing nervous system.These molecules and the cells that express them are under intense study so that we can identify the molecular mechanisms that organize how the nervous system becomes wired together during development.
In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation.
Authors: R E Mandrell, A J Lesse, J V Sugai, M Shero, J M Griffiss, J A Cole, N J Parsons, H Smith, S A Morse, M A Apicella
Journal: The Journal of Experimental Medicine (1990)

After growth of gonococci in the presence of cytidine monophospho-N-acetyl-neuraminic acid (CMP-NANA), their 4.5-kD lipooligosaccharide (LOS) component was increased by approximately 400 daltons, whereas the LOS of strains lacking the 4.5-kD component were unaffected. Expression of mAb-defined epitopes on the 4.5-kD component was decreased on LOS of strains grown in CMP-NANA, and treatment of the LOS with neuraminidase reversed this affect. Gonococci incubated with human PMNs also had decreased expression of the 4.5-kD+ epitopes. A detergent extract of gonococci incorporated radiolabeled NANA in the LOS, suggesting the presence of a sialyltransferase in gonococci. Exogenous sialyltransferases also could use LOS as an acceptor.
Number needed to harm
Authors: P. Sedgwick
Journal: BMJ (2011)

Last week’s question described a trial that assessed the efficacy and safety of varenicline, a smoking cessation aid for users of smokeless tobacco.1 A double blind, placebo controlled, randomised controlled trial was performed. In total, 213 participants were allocated to varenicline and 218 to placebo. Treatment was for 12 weeks, with 14 weeks of follow-up after treatment.2

The primary end point was continuous abstinence from smoking for four weeks at the end of treatment (weeks 9 to 12). Secondary end points included adverse events. One of the most common adverse events was …
Reducing dialysis associated bacteraemia, and recommendations for surveillance in the United Kingdom: prospective study
Authors: Abraham George, Jerome I Tokars, Elaine J Clutterbuck, Kathleen B Bamford, Charles Pusey, Alison H Holmes
Journal: BMJ (2006)

Bacteraemia in dialysis units accounts for major morbidity, mortality, and antibiotic usage. Risk is much greater when lines rather than fistulas are used for haemodialysis. Surveillance is critical for infection control, but no standardised surveillance scheme exists in the United Kingdom.Prospective study in a London dialysis unit of the implementation and applicability of a dialysis associated bacteraemia surveillance scheme developed in the United States and its effect on bacteraemia, antibiotic usage, and admission.Hammersmith Hospital dialysis unit, London, where 112 outpatients receive dialysis three times weekly. Between June 2002 and December 2004, 3418 patient months of data were collected.Successful adoption of the scheme and reductions in bacteraemia rates, antibiotic usage, and admission to hospital. Strategy for improvement Embedding the surveillance scheme in the unit's clinical activity.Raised awareness of bacteraemia prevention, prudent antibiotic prescribing, and the need for improved provision of vascular access. The scheme required two hours a month of consultant time. Significant downward trends were seen in bacteraemia rates and antibiotic usage: mean rate ratios from quarter to quarter 0.90 (95% confidence interval 0.85 to 0.94) and 0.91 (0.87 to 0.96), respectively. The rate of admission to hospital also showed a significant downward trend, with admissions directly connected to access related infection declining more rapidly: mean rate ratio of successive quarters 0.90 (0.84 to 0.96). The overall proportion of patients dialysed through catheters was significantly higher than in US outpatient centres (62.3% v 29.4%, P < 0.01). Study data were successfully used in a business case to improve access provision.Dialysis specific surveillance of bacteraemia is critical to infection control in dialysis units and improving quality of care. Such a scheme could be adopted across the United Kingdom.
The Feminization of Medicine
Authors: Jodi Elgart Paik
Journal: JAMA (2000)

A GENERATION AGO A WOMAN’S ROLE IN MEDICINE WAS THAT OF A patient, and the thought of devoting an entire issue to the subject of gender was unheard of. But much has changed since 1970, when only 8% of practicing physicians and 13% of medical students were women. In the past 30 years, the white coat has opened to increasing numbers of women interested in pursuing a career in medicine. Bytheyear2010,nearlyonethirdofpracticingphysicianswillbewomen. What does that mean for health care? Will the “feminization” of medicine change its practice in the next century? To begin to answer thatquestion,AssistantSurgeonGeneralSusan J.Blumenthal,MD,MPA, delineates the issues and challenges that will confront health care in general, and women’s health in specific, in the new millennium. To understand the historical role of women in medicine, Rhoda Wynn traces their therapeutic image and lineage from ancient times to the present. Today,while84%offemalephysiciansaregenerallysatisfiedwiththeir careers inmedicine, almostone thirdof themwouldnotpursueamedical career if again given the choice. Medicine demands a unique compromise between personal and professional life, but the intensity of job stressors does not appear to vary significantly along gender lines, and the conflicts that may ensue from being both a physician and a parent appeartobelessacauseof jobdissatisfactionthanareworkplace issues— theopportunity for advancement,practicecontrol, andharassment. In an interview with 3 female surgeons, Valerie A. Jones takes a magnifying lens to their lives, both inside and outside the operating room. As women have begun to practice medicine across all specialities, making inroads in organized medicine and academia, the number of female full professors is growing at a rate faster than that of men. Yet women are still underrepresented in leadership positions. Even if the rate of women attaining full professor rank continues to grow yearly as it has during the past 7 years, at least 25 years remain until the proportion of women at full professor rank is half that of men, despite near gender equity when entering medical school. Janet Bickel and Valarie Clark address one remedy to the lagging advancement of women in academic medicine: better mentoring. Finally, this month’s MSJAMA online includes a bibliography from the Women Physicians’ Health Study (WPHS). The WPHS undertakes the challenge of describing who women physicians are and what theybelieve—assessingsuchdifferencesas race, religion, specialtychoice, career satisfaction, and health risks. Data from the WPHS remind us that the generalization “women in medicine” is a rhetorical device, and that female physicians are just as different as they are similar.
Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.
Authors: W M Holleran, E I Ginns, G K Menon, J U Grundmann, M Fartasch, C E McKinney, P M Elias, E Sidransky
Journal: Journal of Clinical Investigation (1994)

Hydrolysis of glucosylceramide by beta-glucocerebrosidase results in ceramide, a critical component of the intercellular lamellae that mediate the epidermal permeability barrier. A subset of type 2 Gaucher patients displays ichthyosiform skin abnormalities, as do transgenic Gaucher mice homozygous for a null allele. To investigate the relationship between glucocerebrosidase deficiency and epidermal permeability barrier function, we compared the stratum corneum (SC) ultrastructure, lipid content, and barrier function of Gaucher mice to carrier and normal mice, and to hairless mice treated topically with bromoconduritol B epoxide (BrCBE), an irreversible inhibitor of glucocerebrosidase. Both Gaucher mice and BrCBE-treated mice revealed abnormal, incompletely processed, lamellar body-derived sheets throughout the SC interstices, while transgenic carrier mice displayed normal bilayers. The SC of a severely affected type 2 Gaucher's disease infant revealed similarly abnormal ultrastructure. Furthermore, the Gaucher mice demonstrated markedly elevated transepidermal water loss (4.2 +/- 0.6 vs < 0.10 g/m2 per h). The electron-dense tracer, colloidal lanthanum, percolated between the incompletely processed lamellar body-derived sheets in the SC interstices of Gaucher mice only, demonstrating altered permeability barrier function. Gaucher and BrCBE-treated mice showed < 1% and < 5% of normal epidermal glucocerebrosidase activity, respectively, and the epidermis/SC of Gaucher mice demonstrated elevated glucosylceramide (5- to 10-fold), with diminished ceramide content. Thus, the skin changes observed in Gaucher mice and infants may result from the formation of incompetent intercellular lamellar bilayers due to a decreased hydrolysis of glucosylceramide to ceramide. Glucocerebrosidase therefore appears necessary for the generation of membranes of sufficient functional competence for epidermal barrier function.
Long-term treatment of plaque psoriasis with efalizumab: an Italian experience
Authors: A. Costanzo, K. Peris, M. Talamonti, A. Di Cesare, M. Concetta Fargnoli, E. Botti, S. Chimenti
Journal: British Journal of Dermatology (2007)

Biologic agents are an important new class of drugs, offering targeted treatment for chronic skin diseases such as psoriasis. The biologic therapy efalizumab is an anti-CD11a monoclonal antibody, which was approved by the European regulatory agency in 2004 for the treatment of moderate-to-severe plaque psoriasis. Here we describe our 2-year experience in treating over 100 patients with moderate-to-severe psoriasis with efalizumab at two dermatology centres in Italy. Overall, we found efalizumab is efficacious for a large subset of patients, regardless of previous therapies received, and has an easily manageable safety profile. We believe one important quality of efalizumab is the stability and maintenance of clinical response over time. We found that most patients who respond to treatment experience a long-term clearing of psoriasis with only mild recurrence events. Our experience with individual cases provides specific insights into efalizumab re-treatment, the use of efalizumab in patients with a history of heart failure, and the management of patients who become pregnant or conceive while receiving efalizumab therapy. In summary, our off-trial experience in over 100 patients confirms the efficacy and safety of efalizumab in the treatment of moderate-to-severe plaque psoriasis.
Effects of Dobutamine on Left Ventricular Performance, Coronary Dynamics, and Distribution of Cardiac Output in Conscious Dogs
Authors: Stephen F. Vatner, Robert J. McRitchie, Eugene Braunwald
Journal: Journal of Clinical Investigation (1974)

The effects of dobutamine ([±]-4-[2-[[3-(p-hydroxyphenyl)-1-methyl propyl] amino] ethyl] pyrocatechol hydrochloride), a new synthetic cardioactive sympathomimetic amine, were examined on direct and continuous measurements of left ventricular (LV) diameter (D), pressures (P), velocity of shortening (V), dP/dt, dP/dt/P, arterial pressure, cardiac output, and regional blood flows in the left circumflex coronary, mesenteric, renal, and iliac beds in healthy, conscious dogs. At the highest dose of dobutamine examined, 40 μg/kg/min, the drug increased dP/dt/P from 65±3 to 128±4 s-1 and isolength velocity from 72±4 to 120±7 mm/s without affecting LV end diastolic D significantly. Mean arterial P rose from 92±2 to 104±3 mm Hg and heart rate from 78±3 to 111±7 beats/min, while LV end systolic D fell from 24.1±1.4 to 19.9±1.8 mm, reflecting a rise in stroke volume from 30±4 to 42±3 ml. Cardiac output rose from 2.41±0.23 to 4.35±0.28 liter/min, while calculated total peripheral resistance declined from 0.042±0.005 to 0.028±0.003 mm Hg/ml/min. The greatest increases in flow and decreases in calculated resistance occurred in the iliac and coronary beds, and the least occurred in the renal bed. Propranolol blocked the inotropic and beta2 dilator responses while vasoconstricting effects mediated by alpha adrenergic stimulation remained in each of the beds studied. When dobutamine was infused after a combination of practolol and phentolamine, dilatation occurred in each of the beds studied. These observations indicate that dobutamine is a potent positive inotropic agent with relatively slight effects on preload, afterload, or heart rate, and thus may be a potentially useful clinical agent. The one property of this drug which is not ideal is its tendency to cause a redistribution of cardiac output favoring the muscular beds at the expense of the kidney and visceral beds.
Medical Writing as Observed by a Reader
Authors: Roger I. Lee
Journal: New England Journal of Medicine (1952)

IT is my privilege to have been intimately acquainted with medical literature for these many years, as both a consistent reader and a not infrequent contributor. Having devoted my attention largely to the original articles, not only in my own field of interest but also in other fields, in the hope of finding out something about the weather on various fronts, I have never had any lasting theories in regard to editorials, reviews of books and articles or special features.The special journals have interested me less and less, for many of the articles contained in them seem unduly long, . . .
P79 Quantifying Physical Activity For 30 Days Via Pedometry in COPD Patients
Authors: AD Alahmari, GC Donaldson, ARC Patel, BS Kowlessar, AJ Mackay, R Singh
Journal: Thorax (2012)

<h3>Introduction</h3> Physical activity and exercise capacity are among the important patient-relevant parameters in COPD. COPD patients are less active and less likely to go outside when compared with the general population and this worsens during exacerbation (1). The aim of this study was to determine whether step-counts measured by a pedometer (Yamax Digi-walker SW-200) would be a useful method of quantifying physical activity in stable COPD patients on the community. <h3>Methods</h3> Stable COPD outpatients wore a pedometer for 30 days, had a six minute walk distance (6MWD) assessed according to ATS protocols and completed the SGRQ (St. George’s Respiratory Questionnaire) and MRC dyspnoea score. The pedometer was worn on the left-hand side during waking hours. Patients recorded daily step counts and time spent outdoors on written daily diary cards. <h3>Results</h3> Fifty-five COPD patients had a mean (±SD) age 70.3 (8.7) years and FEV1 51.0% predicted (±14.1); male gender 67%. The mean (±SD) 6MWD was 416 (±88) metres, with an average of 4327 (±2944) steps/day and spent 3.1 (±1.4) hours outdoors. Figure 1 shows that patients with greater 6MWD took more steps per day during normal activity [r=0.47; p=0.001], Fig. 1A, and stayed outdoors for longer [r=0.41; p=0.003], Fig. 1B. Patients with lower step counts tended to have a poorer health status in terms of SGRQ score[r= –0.31; p=0.025], Fig. 1C, and a higher level of dyspnoea on the MRC score [Rho= –0.39; p=0.005], Fig. 1D. <h3>Conclusions</h3> Daily step counts measured by a pedometer averaged over 30 days correlated well with objective tests of physical capacity, time outdoors, health status and dyspnoea. Thus pedometry is a useful method of quantifying daily physical activity in COPD patients. <h3>References</h3> Donaldson GC <i>et al</i>., Exacerbations and Time Spent Outdoors in Chronic Obstructive Pulmonary Disease, <i>Am J Resp Crit Care Med</i> (2005) 171: 446–452.
Comparison of Single-Dose vs One-Week Course of Metronidazole for Symptomatic Bacterial Vaginosis
Authors: Jay Swedberg
Journal: JAMA (1985)

In a prospective, single-blind, randomized study, a single 2-g dose of metronidazole was compared with a seven-day course of 500 mg given twice daily in the treatment of symptomatic vaginal discharge associated with Gardnerella vaginalis. Based on resolution of symptoms and on cultures negative for G vaginalis, 86% (40/46) of women treated with the single dose and 97% (35/36) of women treated with the seven-day course were considered cured at seven to ten days after treatment. Evaluation at 21 days after treatment, however, indicated that only 46% (16/34) of patients treated with the single 2-g dose were considered cured compared with 86% (26/30) of those treated with the seven-day course. Treatment of sexual contacts did not significantly improve cure rates in either group.
Requirements for the solubilization of immune aggregates by complement. The role of the classical pathway.
Authors: M Takahashi, S Takahashi, V Brade, V Nussenzweig
Journal: Journal of Clinical Investigation (1978)

In this paper we examine the role of the classical pathway in the complement-mediated solubilization of immune precipitates (CRA). Serum reagents were depleted of the alternative pathway components properdin and factor D. Both depleted reagents lack CRA although they have almost intact hemolytic activity. Also, immune complexes were not solubilized when incubated with high concentrations of the classical pathway components (C1, C4, C2, and C3. We conclude that CRA is not mediated by the classical pathway alone. Activation of the classical pathway by the immune aggregates greatly enhances CRA. The effect of the classical pathway is to deposit C3b on the antigen-antibody lattice and promote the assembly of a lattice-associated, properdin-dependent C3-convertase. Although C3, C4, and properdin were detected on complexes solubilized by serum in the presence of Ca++ and Mg++, only C3 and properdin were found on the complexes when Ca++ had been chelated by ethylene glycol-bis-(beta-aminoethyl ether), N,N'-tetraacetic acid. In both situations the aggregates were capable of converting C5 in the fluid phase. However, no C5 was found on the solubilized complexes. These findings suggest that in contrast to nascent C3b and C4b, nascent C5-9 lacks binding affinity for immune aggregates.
OUTCOMES OF MECHANICAL CIRCULATORY SUPPORT FOR REFRACTORY CARDIOGENIC SHOCK IN THE ERA OF MORE ADVANCED VENTRICULAR ASSIST DEVICES
Authors: Hiroo Takayama, Michael Koeckert, Lori Soni, Lauren Truby, Jonathan Yang, Tetsuya Horai, Takeyoshi Ota, Paolo Colombo, Nir Uriel, Ulrich Jorde, Donna Mancini, Yoshifumi Naka
Journal: Journal of the American College of Cardiology (2012)
Broad statements do not tell whole story of prison medicine
Authors: I Jamieson
Journal: BMJ (2002)

EDITOR—I work in custodial medicine and would find abhorrent the idea of referring to my patients, albeit incarcerated, as anything other than my patients. However, the news article by Gulland describing how the NHS is to take over responsibility for prison health services does not tell quite the whole story.1

Obviously differences exist across the service. In my experience a prison doctor sees urgent cases during the same day and around three days routinely. A consultant psychiatrist can be accessed …