tbuckley/cabot-search huggingface dataset:
Cheating at Athens: Is it Worth it?
Authors: Domhnall MacAuley
Journal: BMJ (2004)

<h3>Abstract</h3> The trimeric betaine symporter BetP senses an osmotic upshift via its osmosensory C-terminal domain and responds rapidly with a steep increase in transport rate. Full activation requires both an elevated internal K<sup>+</sup> concentration and a yet unknown membrane stimulus. Moreover, the molecular mechanisms of stress sensing and upregulation remain unclear. Here, we show that K<sup>+</sup> binding to BetP <i>in vivo</i> is highly cooperative. Using X-ray crystallography, we identify four putative K<sup>+</sup> interaction sites at the C-terminal domains of BetP. Single particle CryoEM on BetP reconstituted in amphipols (AMP-BetP), in the absence of K<sup>+</sup>, revealed that the three C-terminal domains are oriented symmetrically near the membrane surface, representing a new downregulated state. The presence of K<sup>+</sup> resulted in asymmetric partial unfolding of the C-terminal domains, which was assigned as an intermediate between the downregulated state and the conformation observed in crystal structures. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy in 2D crystals of BetP reveal glutamate/aspartate and tyrosine responses to K<sup>+</sup>, in agreement with the identified K<sup>+</sup> interaction sites, as well as specific unfolding events in the C-terminal domain upon activation. A rearrangement of the relative protomer orientations confers upregulation through key structural elements involved in the alternating access of BetP affecting sodium and betaine binding affinities. Although K<sup>+</sup>-specific regulation is unique to BetP we discuss unfolding/refolding of sensory domains as a unifying element in hyperosmotic stress response of osmoregulated transporters.
Recruitment of CD1a+ Langerhans cells to the nasal mucosa in seasonal allergic rhinitis and effects of topical corticosteroid therapy
Authors: S. J. Till, M. R. Jacobson, F. O'Brien, S. R. Durham, A. KleinJan, W. J. Fokkens, S. Juliusson, O. Lowhagen
Journal: Allergy (2001)

Background: Local antigen presentation may be necessary for both primary and recall T‐cell responses to grass pollen in hay fever patients. We examined the effect of seasonal allergen exposure on nasal mucosal antigen‐presenting cell (APC) populations and the effects of topical corticosteroid therapy. Methods: Nasal biopsies were collected from 46 grass pollen‐sensitive seasonal rhinitis patients before the grass‐pollen season. A second biopsy was collected during the pollen season, when patients had received 6 weeks' treatment with either fluticasone propionate (200 µg, twice daily) or placebo. Cell populations in biopsy sections were quantified by immunocytochemistry. Results: Significant increases in submucosal and epithelial CD1a+ Langerhans cells, but not CD68+ macrophages or CD20+ B cells, were observed during the pollen season. Seasonal increases in CD1a+ Langerhans cells were inhibited by corticosteroid therapy. Conclusions: Recruitment of CD1a+ Langerhans cells to the nasal mucosa during natural seasonal allergen exposure may contribute to local T cell responses. Topical corticosteroids may act, at least in part, by inhibiting effective allergen presentation to T cells through inhibition of recruitment of Langerhans cells to the nasal mucosa.
Eruptive seborrhoeic keratosis in human immunodeficiency virus infection: a coincidence or 'the sign of Leser-Trelat'?
Authors: A.C. Inamadar, A. Palit
Journal: British Journal of Dermatology (2003)

Journal Article Eruptive seborrhoeic keratosis in human immunodeficiency virus infection: a coincidence or 'the sign of Leser‐Trélat'? Get access A.C. Inamadar, A.C. Inamadar Department of Dermatology, Venereology and Leprology, BLDEA's SBMP Medical College, Hospital and Research Centre, Bijapur 586103, Karnataka, India E‐mail: aparuna1@rediffmail.com Search for other works by this author on: Oxford Academic Google Scholar A. Palit A. Palit Department of Dermatology, Venereology and Leprology, BLDEA's SBMP Medical College, Hospital and Research Centre, Bijapur 586103, Karnataka, India E‐mail: aparuna1@rediffmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 2, 1 August 2003, Pages 435–436, https://doi.org/10.1046/j.1365-2133.2003.05463.x Published: 01 August 2003
Archives of Family Practice: Selected Papers and Abstracts Representing Original Work Advancing the Specialty of Family Practice
Authors: Chris Meuli
Journal: JAMA (1981)

The<i>Archives</i>is the first volume of what will become an annual collection of original articles and abstracts reviewing the clinical, educational, and research developments of the new specialty of family practice. In the past, this specialty has lacked its own traditions of literature, education, and research because the other specialties have provided this information and training for the generalist. This collection of articles is broken up into three distinct sections. The first section considers the development of family practice as a specialty in its historical progression as a unique field of study with a well-defined body of knowledge. This includes articles that were instrumental in the philosophic evolution of family practice in the early 1960s and more recent evaluations showing how family practice contributes a novel and valuable approach to clinical research. The second section deals with the development of undergraduate education programs in family medicine during the past
EVALUATION OF APICAL SUBTYPE OF HYPERTROPHIC CARDIOMYOPATHY USING CARDIAC MRI WITH GADOLINIUM ENHANCEMENT
Authors: Kalie Yang Kebed, Raed Al Adham, Kalkidan Bishu, John Askew, Kyle Klarich, Philip Araoz, Thomas Foley, James Glockner, Rick Nishimura, Steve Ommen, Nandan Anavekar
Journal: Journal of the American College of Cardiology (2013)
RM-06 * IN VITRO CLONAL EVOLUTION OF GLIOBLASTOMA (GBM) BRAIN TUMOUR INITIATING CELLS (BTIC) TO MODEL TUMOUR RECURRENCE
Authors: M. Qazi, P. Vora, C. Venugopal, N. McFarlane, R. Hallett, S. Singh
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM) is the most common and highly aggressive primary adult brain tumour. Despite multimodal therapy, patients on average experience relapse at 9 months and median survival rarely extends beyond 15 months. Targeting the cells that drive GBM formation as well as its inevitable and rapid recurrence has remained a major challenge, likely due to intra-tumoral heterogeneity. At the genetic level, this heterogeneity has prompted a molecular classification of GBM based on differential transcriptome profiling by TCGA. At the cellular level, this heterogeneity may be explained by the existence of multiple subpopulations of cancer cells that have acquired stem cell properties, termed brain tumour initiating cells (BTICs). We postulate that different BTIC subpopulations are capable of first initiating the tumor, and later evading therapy to seed the tumor relapse or recurrence, as they undergo clonal evolution over time in response to various environmental cues including chemotherapy and radiotherapy. In this study, we developed a novel in vitro BTIC model to profile the clonal evolution of treatment naïve GBM BTICs through therapy (temozolomide and radiation treatment) based on transcriptome analysis, stem cell assays and BTIC protein marker expression (CD133, CD15, Sox2 and Bmi1). The expression profile of in vitro treated GBM was compared to recurrent GBM patient samples to determine if our model recapitulated clonal BTIC evolution as seen in patients. Profiling the dynamic nature of BTICs and their evolution over the course of treatment and tumour progression may offer novel therapeutic targets for the treatment of primary and recurrent GBM.
Ocular Nerve Palsy with Severe Headache in Diabetics
Authors: W. P. U. Jackson
Journal: BMJ (1955)

The US Food and Drug Administration’s approval of a peanut oral immunotherapy product in January 2020 is a landmark development in the field of food allergy therapy. While food allergy prevalence has been increasing, this product is the first approved therapy for food allergy. Oral immunotherapy has many similarities to subcutaneous immunotherapy and drug desensitization protocols, but does not lead to sustained unresponsiveness. The studies leading to approval of the Palforzia product demonstrated increase in the amount of peanut protein able to be consumed, with 67% of subjects randomized to the treatment arm able to consume 600 mg of peanut protein in double-blind placebo-controlled food challenge at study exit. However, side effects are an important consideration, and dropout rates in studies of Palforzia ranged from 11% to 21%. Postmarketing surveillance of this product will be critical in assessing its long-term risks and benefits.
Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells.
Authors: D B Lewis, C C Yu, J Meyer, B K English, S J Kahn, C B Wilson
Journal: Journal of Clinical Investigation (1991)

The mechanisms by which T lymphocytes acquire the capacity to produce interleukin 4 (IL-4) and other lymphokines during intrathymic and extrathymic development are poorly understood. To gain insight into this process, we determined the capacity of human neonatal and adult T lineage cell populations to produce IL-4 after polyclonal activation. IL-2 and interferon-gamma (IFN-gamma) production were studied in parallel, since their production by neonatal T cells is known to be similar or diminished, respectively, compared to adult T cells. Production of IL-4 by neonatal CD4+ T cells and IFN-gamma by neonatal CD4+ and CD8+ T cells was markedly lower compared with analogous adult cell populations, whereas IL-2 production was similar. Transcription of IL-4, as determined by nuclear run-on assays, and IL-4 mRNA-containing cells, as determined by in situ hybridization, were undetectable in neonatal T cells, whereas both were detectable in adult T cells. IFN-gamma transcription and IFN-gamma mRNA-containing cells were reduced in neonatal T cells compared with adult T cells. Reduced lymphokine production by neonatal T cells correlated with their lack of a CD45R- (putative memory T cell) population; cells with this surface phenotype comprised 30-40% of the adult CD4+ T cells and were highly enriched for IL-4 and IFN-gamma, but not IL-2 production. IL-4, IFN-gamma, and IL-2 mRNA expression by neonatal CD4+CD8- thymocytes was similar to that found in circulating neonatal CD4+ T cells. Taken together, these findings suggest that the extrathymic generation of memory T cells during postnatal life may result in an increased capacity for IL-4 and IFN-gamma gene expression. In addition, IFN-gamma and IL-2 mRNA were significantly more abundant than IL-4 mRNA in activated neonatal CD4+CD8- thymocytes and CD4+ T cells, as well as adult CD4+ CD45R- T cells. Therefore, the capacity of T lineage cells to express the IL-4 gene may be more restricted compared to other lymphokine genes beginning in intrathymic development. This restricted capacity appears to persist during postnatal extrathymic maturation of T cells.
Shelter and indoor air.
Authors: J A Stolwijk
Journal: Environmental Health Perspectives (1990)

Improvements in outdoor air quality that were achieved through the implementation of the Clean Air Act accentuate the quality of the indoor air as an important, if not dominant, factor in the determination of the total population exposure to air contaminants. A number of developments are adding important new determinants of indoor air quality. Energy conservation strategies require reductions in infiltration of outdoor air into buildings. New materials introduced in the construction and in the maintenance of buildings are contributing new air contaminants into the building atmosphere. Larger buildings require more and more complex ventilation systems that are less and less under the individual control of the occupants. All of these factors contribute to the current reality that indoor air contains more pollutants, and often at higher concentrations, than outdoor air. Especially in the larger buildings, it will be necessary to assure that an adequate quantity of fresh air of acceptable quality is provided to each individual space, and that no new sources of pollutants are added to a space or a whole building without appropriate adjustments in the supply of fresh air.
Viagra makes flowers stand up straight
Authors: J. Siegel-Itzkovich
Journal: BMJ (1999)

Viagra (sildenafil citrate) is good not only for treating male impotence Israeli and Australian researchers have discovered that small concentrations of the drug dissolved in a vase of water can also double the shelf life of cut flowers, making them stand up straight for as long as a week beyond their natural life span.

They have already tested Viagra on strawberries, legumes, roses, carnations, broccoli, and other perishables. In this latest research they found that 1 mg of the …
903 OMEGA-3 FATTY ACIDS AND/OR FLUVASTATIN IN HEPATITIS C PRIOR NON-RESPONDERS TO COMBINATION ANTI-VIRAL THERAPY – A PILOT RANDOMISED CLINICAL TRIAL
Authors: D.A. Sheridan, S.H. Bridge, M.M.E. Crossey, D.J. Felmlee, F. Fenwick, H.C. Thomas, D. Neely, S.D. Taylor-Robinson, M.F. Bassendine
Journal: Journal of Hepatology (2013)
HTLV-I/II Infection in Women With Acute Pelvic Inflammatory Disease
Authors: Sharon Safrin, Valerie L. Ng, Michael S. McGrath, Bonnie J. Dattel, Laurie Hauer, Richard L. Sweet
Journal: JAMA (1990)

<h3>To the Editor.—</h3> We studied the seroprevalence of human T-cell lymphotropic virus type I/II (HTLV-I/II) antibody in 333 women admitted to San Francisco General Hospital with acute pelvic inflammatory disease between January 1985 and December 1988. Testing was limited to banked serum samples from women who had enrolled in antibiotic research studies, representing 45% of women admitted with acute pelvic inflammatory disease during this period. Antibody to chromatographically purified (C91/PL) HTLV-I was detected by immunoblot; reactivity with p24 and p19 was confirmed by two separate observers. Seroprevalence of HTLV-I/II was 3.0% (95% confidence interval, 1.2% through 4.8%). There was no evidence of increasing prevalence of infection during the 4-year time span: 2 (12.5%) of 16 patients in 1985, 4 (3.9%) of 103 in 1986,4 (4.2%) of 95 in 1987, and 0 (0%) of 119 in 1988. In this same sample, seroprevalence of human immunodeficiency virus type 1 was 4.2% (95%
SOME CONSIDERATIONS OF THE SYMPTOMATOLOGY IN THE DIAGNOSIS OF TABES.
Authors: J. M. AIKIN
Journal: JAMA (1898)

walk with the aid of crutches.Superficial pressure over the spine in the lower dorsal, lower lumbar and sacral regions and also over the coccyx induced pain, and deep pressure over the muscles of the back of the trunk in the lower dorsal and lumbar regions on the left side, and in less degree on the right side, elicited tenderness.Similar tenderness was noted also on the left side of the chest.Transmitted shock caused pain referred to the lumbar region, flexion of the trunk pain referred to the same region, and especially lateral flexion to the left.Attempts to extend the legs, with the patient seated on a chair, induced pain referred to the back of the legs and thighs.The knee-jerks were exaggerated.There was some analgesia of the left arm, left leg and left side of the trunk, but no inflammatory or ovarian tenderness, and no limitation of the visual fields.
Inhaled misoprostol blocks guinea pig antigen-induced bronchoconstriction and airway inflammation.
Authors: W G Smith, J M Thompson, D L Kowalski, J P McKearn
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Inhaled E-type prostaglandins (PGE) have been shown to modulate responses to both allergic and nonallergic provocation. Misoprostol, a PGE1 analog, was developed as an antiulcer agent because it prevents gastrointestinal ulceration. Little is known about the effect inhaled misoprostol has on the airway and whether its potential antiasthmatic activity would be similar to other PGEs. Nebulizied solutions of misoprostol and PGE2 effectively blocked the acute bronchospasm caused by a subsequent inhaled antigen challenge in actively sensitized guinea pigs. The minimal concentration to result in a significant reduction in specific airway resistance was 3 and 30 micrograms/ml for misoprostol and PGE2, respectively. Exposure to a 300 micrograms/ml nebulized misoprostol solution provided significant protection for 2 h. Eosinophil recovery in bronchoalveolar lavage performed 24 h after antigen challenge was significantly reduced by 72%. In a chronic model of antigen-induced airway inflammation in which guinea pigs are given multiple antigen exposures over a 3-wk period, both misoprostol and its free acid-active metabolite 5C-30695 significantly reduced bronchoalveolar lavage eosinophils by 50 to 55%. Treatment with TRFK5, a monoclonal antibody to interleukin-5, resulted in a 76% decrease in eosinophil recovery. The combination of antibronchoconstrictive and anti-inflammatory effects suggests that inhaled misoprostol may be an effective treatment for the acute and chronic symptoms of asthma.
The Permeability of Excised Arteries and Other Tissues to Serum Lipid
Authors: SIGMUND L. WILENS, ROBERT T. McCLUSKEY
Journal: Circulation Research (1954)

Excised arterial tissue is shown to differ from other excised tissues by its property of retaining fractions of serum lipids that are transfiltered under pressure in the form of zonal deposits at the elastic tissue membranes. The mode of deposition of artificially produced lipid accumulations and spontaneously formed ones is probably very similar. Various factors that influence the deposition of lipid in excised arteries are examined in detail. The most important of these prove to be the structural peculiarities of arterial tissue and the concentration of lipid in the serum.
Observational study of a general practice out of hours cooperative: measures of activity
Authors: C. Salisbury
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To evaluate an out of hours cooperative of general practitioners compared with a deputising service. <b>Design:</b> Observational study of two services in overlapping geographical areas. <b>Setting:</b> A general practice cooperative in Kensington, Chelsea, and Westminster and a deputising service operating in that area and the neighbouring area of Brent and Harrow. <b>Subjects:</b> All patients contacting a doctor at either service in an eight week period beginning 1 September 1995. <b>Main outcome measures:</b> Patients9 age and sex; rates of home visiting, telephone advice, and attendance at a primary centre; hospital admission rates; prescribing rates; times of patient calls; and response times. <b>Results:</b> Data were collected on 5812 patient contacts. Doctors from the cooperative visited 32.0% (1253/3920) of patients, offered telephone advice to 57.8% (2267), and saw 7.1% (278) of patients at the primary care centre. By contrast, the deputising service visited 76.3% (1444/1892) of patients and gave telephone advice to 19.3% (365). Doctors from the cooperative prescribed drugs to fewer patients (37.6%; 1473/3915) than did the deputising service (51.7%; 941/1821) (odds ratio 0.56 (95% confidence interval 0.50 to 0.63) adjusted for age and sex) and admitted 8.7% (339/3888) of patients to hospital compared with 6.8% (128/1889) from the deputising service (odds ratio 1.30 (1.05 to 1.61) adjusted for age and sex). Response times for the deputising service were faster (median time to visit 65 minutes) than for the cooperative (median time to visit 75 minutes) but the time to first contact with a doctor was shorter for the cooperative because most people initially received telephone advice. <b>Conclusions:</b> The cooperative in this study dealt with patient contacts very differently from the way the deputising service dealt with contacts, fewer patients being visited and fewer receiving prescriptions. The data presented enable other out of hours services to compare their own performance using a standard data collection and analysis program. <h3>Key messages</h3> A primary care out of hours cooperative dealt with patients9 calls very differently from an established deputising service, which may have important implications for patient satisfaction and expectations Randomised controlled trials are very difficult to conduct to evaluate established services but could be planned before introducing a new service The impact of a high rate of out of hours telephone advice on health outcomes should be a priority for future research Few patients are currently willing or able to attend an out of hours primary care centre in London Standard indicators and measurement tools should be defined to evaluate different models of out of hours care, and the results of an annual evaluation of local providers should be made available to general practitioners
Case 50-1961
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. Kibbee
Journal: New England Journal of Medicine (1961)

Presentation of Case A sixty-year-old woman entered the hospital because of epigastric pain. Four months previously she experienced the onset of constant, aching epigastric pain that was associated with heartburn and eructation and relieved by food or alkali. There were no tarry stools, nausea or vomiting. Seven weeks before entry a stool specimen gave a ++++ guaiac test, and the hemoglobin was 9.5 gm. per 100 ml. An upper gastrointestinal series at that time demonstrated moderate deformity of the duodenal cap and convergence of the mucosal folds, with a small pooling of barium. With a bland diet and antacids she . . .
Colonic stenting: a palliative measure only or a bridge to surgery?
Authors: T. Baron
Journal: Endoscopy (2010)

Self-expandable metal stents (SEMS) are used to relieve malignant luminal obstruction throughout the gastrointestinal tract. Colonic SEMS are used most often for palliation of obstruction in nonoperative candidates or in patients with advanced disease. The other indication for colonic stent placement is as a preoperative modality for the relief of acute obstruction so that resection can be done on an elective basis after stabilization of the acute illness and bowel preparation. For both of these indications, the goal is avoidance of a temporary or permanent ostomy. In this manuscript the supporting data for each of these indications will be reviewed.
Hubert Cedric Burnell
Authors: J C Burnell
Journal: BMJ (2004)

Former general practitioner Wednesbury, West Midlands (b Bangor, north Wales, 1917; q Birmingham 1941), died from coronary artery disease on 13 May 2003.​2003.




Figure 1




After qualifying he was immediately drafted into the army, serving in north Africa and Italy during the second world war. He returned to the Birmingham area, where he did hospital jobs before taking up general practice in Wednesbury from 1947 until 1977. He then worked part time as a medical assessor for the Department of Health and Social Security. His interests ranged from gardening and ornithology to water colour painting and learning to speak Welsh. He leaves a wife, Margaret; three sons; and eight grandchildren.
Aerosols and Aerosol Propellants in Asthma
Authors: Millard Bass
Journal: JAMA (1971)

To the Editor.—  The inspired mixture of fluorocarbon may contribute to a  state in the experimental animal not only by an impediment to diffusion of oxygen through the dense inert gaseous medium prevailing in the airway but also by altering the ventilation perfusion relationships. Chouteau and co-workers 1,2 in France have observed the hypoxic crisis in goats exposed to argon, nitrogen, and helium in a diving chamber with simulated depths up to 3,000 feet. Some of the animals exhibited a phenomenon of sudden collapse associated with abnormal neurological activity even though in each instance the oxygen tension (Po 2 ) was maintained at the equivalent level of air at the surface. When untoward neurologic signs did occur, raising the inspired Po 2 led to a reversal of the neurologic deficit and the animals then behaved normally to inspection.  Concerning the potential danger of pressurized aerosol spray, the victim of an