tbuckley/cabot-search huggingface dataset:
Osteopontin: a bridge between bone and the immune system
Authors: Ellen M. Gravallese
Journal: Journal of Clinical Investigation (2003)

The molecular mechanisms underlying the putative role of osteopontin in the chronic inflammatory disease rheumatoid arthritis are unclear. A study in a murine model of arthritis now demonstrates that a specific antibody directed against the exposed osteopontin epitope SLAYGLR is capable of preventing inflammatory cell infiltration in arthritic joints.
Abstract 4552: Naturally occurring osmolyte, trehalose induces a functionally active conformation in an intrinsically disordered transactivation function domain (AF1) of the Glucocorticoid Receptor
Authors: Shagufta H. Khan, John A. Arnott, Hani Atamna, Nihal Ahmad, Raj Kumar
Journal: Cancer Research (2011)

Abstract Due to the ability of glucocorticoids to prevent the growth and to cause apoptotic death of malignant cells, they are a mainstay of therapy for many lymphomas and leukemias. Glucocorticoid receptor (GR) mediates the biological effects of glucocorticoids at the level of gene regulation. To initiate transcription of target gene(s), GR interacts with its response element DNA, and/or with various coregulatory proteins. However, specific interaction surfaces of GR with its coregulators are not well understood. Consequently, precisely how transcription is regulated by GR is largely unknown. This is due, in part, to the lack of information about GR's major transactivation function region, AF1 located in the N-terminal domain. The major obstacle in determining the structure of AF1 has been due to its intrinsically disordered (ID) conformation, frequently found in the activation domains of many transcription factors, and it is believed that ID nature of these activation domains promote molecular recognition by creating large interaction surfaces suitable for interactions with their specific protein binding partners, which is a critical component of gene regulation by transcription factors. It has been hypothesized that conditional folding of these activation domains may be a prerequisite for their efficient interaction with specific coregulatory proteins, and subsequent transcriptional activity leading to the regulation of target gene(s). In this study, we tested whether a naturally occurring osmolyte, trehalose can promote functionally ordered conformation in the GR's major activation function domain, AF1, which is found to exist as an ID protein, and requires an efficient interaction with coregulatory proteins for optimal activity. Our data show that trehalose induces an ordered conformation in AF1 such that its interaction with steroid receptor coactivator-1 (SRC-1), a critical coregulator of glucocorticoid receptor's activity, is greatly enhanced. Our results may provide a mechanism for cell-type specificity of the effects of GR in gene regulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4552. doi:10.1158/1538-7445.AM2011-4552
Left Ventricular Pressure-Volume Characteristics in Congenital Heart Disease
Authors: M. M. JARMAKANI, SAM B. EDWARDS, MADISON S. SPACH, RAMON V. CANENT, M. PAUL CAPP, MARY J. HAGAN, ROGER C. BARR, VISHNU JAIN
Journal: Circulation (1968)

The continuous pressure-volume relationships throughout the cardiac cycle were evaluated in children with tetralogy of Fallot, isolated ventricular septal defect, and patent ductus arteriosus. Biplane cineangiocardiography and simultaneous left ventricular pressures were utilized for data acquisition. Normal pressure-volume loops demonstrated only small changes in left ventricular volume during the isovolumic periods. In tetralogy of Fallot, there was a decrease in left ventricular volume during the interval of the "isovolumic" contraction with 12 to 43% of the total stroke volume being ejected during this phase. A decrease in left ventricular volume during this time was also found in large ventricular septal defects; however, volume changes during this interval were minimal in those patients judged to have small defects. With large left-to-right shunts of comparable magnitude, the relative area of the pressure-volume loop was greater in patent ductus arteriosus as compared with ventricular defects. Both conditions demonstrated marked increase in stroke volume, with peak systolic pressures rising higher in those patients with patent ducus arteriosus as compared to those with ventricular septal defect.
Association between air pollution exposure and exhaled nitric oxide in an elderly population
Authors: G Adamkiewicz
Journal: Thorax (2004)

Animal models suggest that the cardiovascular effects of air pollution result in part from inflammation caused by proinflammatory mediators originating in the lung. In a human study of the cardiovascular effects of air pollution, we aimed to evaluate the potential association between air pollution levels and the fraction of exhaled nitric oxide (FE(NO)), a non-invasive measure of airway inflammation.Breath samples were collected weekly between September and December 2000 in a community based group of elderly subjects (median age 70.7 years) in Steubenville, Ohio. The samples were analysed for NO. Air pollution levels were measured concurrently at a central site monitor.An increase in the 24 hour average PM(2.5) concentration of 17.7 micro g/m(3) was associated with an increase in FE(NO) of 1.45 ppb (95% CI 0.33 to 2.57) in models adjusted for subject, week of study, day of the week, hour of the day, ambient barometric pressure, temperature, and relative humidity. This represents a change of approximately 15% compared with the mean FE(NO) in the cohort (9.9 ppb). A significant association was also observed for a 24 hour moving average of ambient NO (0.83 ppb increase, 95% CI 0.26 to 1.40). In two-pollutant models, the magnitude and precision of the PM(2.5) effect was not reduced and the ambient NO effect was no longer significant. The associations between FE(NO) and PM(2.5) were significantly higher in subjects with a doctor's diagnosis of COPD (p value for interaction = 0.03).Ambient pollution may lead to airway inflammation as measured by FE(NO). These subclinical inflammatory changes may be an important step in the pathogenesis of the cardiopulmonary effects induced by exposure to air pollution.
The extrathyroidal conversion rate of thyroxine to triiodothyronine in normal man
Authors: Constance S. Pittman, Joseph B. Chambers, Virginia H. Read
Journal: Journal of Clinical Investigation (1971)

Eight normal subjects were administered tracer amounts of a (14)C-labeled thyroxine, L-[tyrosyl-(14)C] T(4), by multiple injections. Then serial blood samples were collected for isolation of the thyroxine, triiodothyronine, and tetraiodothyroacetic acid fractions by a combination of column and paper chromatographies. The chromatographic artifacts were corrected by adding to the sera a purified (3)H-labeled thyroxine, D,L-[alpha,beta-(3)H] T(4) immediately after the separation of sera from blood. 1-2% of the serum (14)C radioactivity was observed in the triiodothyronine fraction and 2-4% of the serum (14)C radioactivity was observed in the tetraiodothyroacetic acid fraction. Complete kinetic studies of thyroxine and triiodothyronine were compared in the same individual in four of the subjects. The extrathyroidal conversion rates of thyroxine to triiodothyronine were calculated from data obtained during both the injection and the postinjection periods as functions of the (14)C-labeled thyroxine and triiodothyronine remaining in the body at time t and their fractional turnover rates. The average daily rate of the extrathyroidal conversion of thyroxine to triiodothyronine was 4% of the extrathyroidal thyroxine pool or 33% of the total thyroxine production. The amount of triiodothyronine generated by this pathway (22 mug/day) was found to contribute 31% of the extrathyroidal triiodothyronine pool or 41% of the daily triiodothyronine production. This pathway is a major source of triiodothyronine production. The extrathyroidal conversions of thyroxine to triiodothyronine and tetraiodothyroacetic acid are major metabolic pathways of thyroxine in normal man.
CELLS INVOLVED IN THE IMMUNE RESPONSE
Authors: Fritz Daguillard, Maxwell Richter
Journal: The Journal of Experimental Medicine (1969)

Cells of the different lymphoid organs in the normal adult rabbit were investigated for their capacity to respond in vitro to a number of stimuli, such as phytohemagglutinin (PHA), anti-rabbit immunoglobulin antiserum (GARIG) and allogeneic and xenogeneic lymphoid cells, and for their capacity to adsorb radioactively-labeled anti-immunoglobulin antiserum. The bone marrow cells responded minimally to PHA, GARIG, and the allogeneic and xenogeneic stimuli. The thymus cells were unable to respond to stimulation with GARIG although they responded to the other stimuli. The cells of the other lymphoid organs tested responded to all the mitogenic agents, to varying degrees. On the basis of the results presented and the findings of other investigators, it is concluded that: 1. The response of the cells to GARIG indicates a potential capacity to mediate humoral immunity and requires the presence of immunoglobulin or immunoglobulin-like recognition sites on the cell surface. 2. The response of the cells to PHA and allogeneic and xenogeneic cells indicates a potential capacity to mediate cellular immunity and does not necessitate the presence of immunoglobulin-recognition sites on the cell surface. 3. The thymus in the normal adult rabbit consists of cells capable of mediating cellular immunity only. 4. The other lymphoid organs appear to possess cells capable of mediating humoral and cellular immunity.
Single-beat estimation of the slope of the end-systolic pressure-volume relation in the human left ventricle.
Authors: M Takeuchi, Y Igarashi, S Tomimoto, M Odake, T Hayashi, T Tsukamoto, K Hata, H Takaoka, H Fukuzaki
Journal: Circulation (1991)

This study assessed a new method of estimating the slope (Ees) of the end-systolic pressure-volume relation (ESPVR) from a single beat of the human heart. Left ventricular pressure was recorded with a high-fidelity micromanometer in patients with heart disease during left ventriculography. Peak isovolumic pressure at the end-disastolic volume was estimated by a curve-fitting technique from an isovolumic left ventricular pressure curve. The ESPVR line was drawn from the estimated peak isovolumic pressure-volume point tangential to the left upper corner of the pressure-volume loop. The slope of this estimated ESPVR line from single-beat analysis was compared with the slope of the ESPVR line obtained from three pressure-volume loops in 16 patients given angiotensin II or nitroglycerin infusion. The estimated Ees was 5.0 +/- 2.2 mm Hg/ml/m2, and the conventional Ees was 4.9 +/- 2.7 mm Hg/ml/m2. The estimated Ees showed a positive correlation with the conventional Ees (r = 0.91, p less than 0.001, SEE = 1.2 mm Hg/ml/m2). In the other 13 patients, after dobutamine infusion (5 micrograms/kg/min i.v.) the estimated Ees increased significantly from 5.6 +/- 1.4 to 7.4 +/- 2.0 mm Hg/ml/m2 (p less than 0.01). Thus, the estimated Ees approximated the conventional Ees and was sensitive to a positive inotropic intervention. We conclude that this single-beat analysis method facilitates assessment of the beat-by-beat ESPVR of the human heart.
Internet supplier of fake Viagra is ordered to pay back 14.4m
Authors: C. Dyer
Journal: BMJ (2012)

A British fraudster who sold fake sildenafil (Viagra) and slimming pills over the internet has been ordered to pay back a record £14.4m after one of the biggest investigations to be undertaken by the Medicines and Healthcare Products Regulatory Agency (MHRA).

Southwark Crown Court in London ordered Martin Hickman, 52, to pay the sum within six months or face a further 10 years in prison.

Investigators found that he had acquired extensive assets, including a house in Ashton under Lyne, Staffordshire, several luxury flats, …
Surveying the literature from animal experiments
Authors: Roger Lemon, Stephen B Dunnett
Journal: BMJ (2005)

Resistance to multiple antibiotics in S aureus is a problem that all prescribers should consider if we are to preserve our capability to treat infections.However, we need to understand that what we are trying to control is the spread of the bacteria, which are already resistant to most antibiotics, rather than the initial emergence of resistance.With that in mind, prescription must be part of a package that includes infection control and the implementation of hygiene barriers that prevent the cross infection of patients.Only then would we have any prospect to reduce resistance sufficiently to allow us to reintroduce the antibiotics we used earlier. 10We also need to remember that antibiotic treatment for Gram positive bacteria is often less effective at controlling Gram negative bacteria.Some strains are pan-resistant and are now at least as difficult to control as MRSA, and it would be ironical if we defer one problem only to have to confront a worse one.
Alprenolol: An Effective Beta Blocker for Digitalis-Induced Ventricular Arrhythmias.
Authors: R. L. Batey
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Alprenolol: An Effective Beta Blocker for Digitalis-Induced Ventricular Arrhythmias.R. L. Batey, M.D., L. J. Lieberman, M.D., R. S. Eliot, M.D., F.A.C.P.R. L. Batey, M.D.Search for more papers by this author, L. J. Lieberman, M.D.Search for more papers by this author, R. S. Eliot, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-778_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDigitalis-induced cardiac arrhythmias remain a significant therapeutic problem. Recently beta-adrenergic blocking agents have been used. However, although propranolol suppresses certain types of supraventricular arrhythmias resulting from over-digitalization, it has not been shown to be equally effective in suppressing ventricular arrhythmias. The cardiovascular effects of a new beta-adrenergic blocking agent, alprenolol, (Aptine®, Astra Pharmaceutical Products, Inc., Worcester, Mass.), are similar to propranolol. The major difference is that alprenolol has a direct cardiac beta-adrenergic effect This additional effect should theoretically reduce the incidepce and degree of severe bradycardia, hypotension, and heart failure. Alprenolol was used in nine instances of digitalis-induced ventricular arrhythmias.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Gainesville, Fla. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByGlykoside 1 May 1970Volume 72, Issue 5Page: 778-778KeywordsArrhythmiaBradycardiaHeart failureHypotension Issue Published: 1 May 1970 PDF DownloadLoading ...
Points: Ophthalmic services in the NHS
Authors: H H E Batten, A S Playfair
Journal: BMJ (1979)

This would perhaps bring home to the DHSS the extent to which the consultants are financ- ing the Health Service by running their own cars.I personally as a consultant manage to run one mini.My wife wonders why I spend all this money running a car for the sake of the NHS when she never has the use of it.I feel that the time has come now for my wife to have the use of our car and to insist that the hospital provides transport when it is needed.
Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials
Authors: David P Dearnaley, Malcolm D Mason, Mahesh KB Parmar, Karen Sanders, Matthew R Sydes
Journal: The Lancet Oncology (2009)

Bisphosphonates might modulate the development of symptomatic bone metastases in men with prostate cancer. The Medical Research Council (MRC) PR05 and PR04 randomised controlled trials assessed the use of sodium clodronate, an oral, first-generation bisphosphonate. We report the final analyses of long-term survival data with additional follow-up in both trials.311 men with metastatic disease were recruited to PR05 between 1994 and 1998, and 508 men with non-metastatic disease were recruited to PR04 from 1994 to 1997. All men were treated according to the recruiting site's standard practice at the time: for metastatic disease, all men were starting or responding to long-term hormone therapy; for non-metastatic disease, most men had radiotherapy, hormone therapy, or both. Men were randomly assigned to take four tablets per day of sodium clodronate (2080 mg) or matching placebo for up to 3 years (metastatic disease) or 5 years (non-metastatic). Long-term overall survival was assessed on an intention-to-treat basis in all men at sites in England and Wales using data from the National Health Service Information Centre, which held data for 278 of 311 men in the PR05 trial and 471 of 508 men in the PR04 trial. These studies are registered International Standardised Randomised Controlled Trials, numbers ISRCTN38477744 (PR05) and ISRCTN61384873 (PR04).Of the 278 men with metastatic disease, 258 (93%) were reported to have died. Evidence of a benefit for those with metastatic disease from use of sodium clodronate compared with placebo was seen in overall survival (hazard ratio [HR] 0.77, 95% CI 0.60-0.98; p=0.032). Of the 471 men with non-metastatic disease, 281 (60%) were reported to have died, with no evidence of improvement in overall survival with clodronate compared with placebo (HR 1.12, 0.89-1.42; p=0.94).Long-term data from these trials show that a first-generation bisphosphonate, sodium clodronate, improves overall survival in men with metastatic prostate cancer who are starting hormone therapy, but there is no evidence of an effect in men with non-metastatic prostate cancer.UK MRC; and an education grant and free drug from Roche Products Ltd.
National Study of Internal Medicine Manpower XVIII: Subspecialty Fellowships with a Special Look at Hematology and Oncology, 1988-1989
Authors: Christopher S. Lyttle, Ronald M. Andersen, Kristen Neymarc, Christian Schmidt, Claire H. Kohrman, Gerald S. Levey
Journal: Annals of Internal Medicine (1991)

Objective: To determine the number and distribution of internists in subspecialty training and compare with data collected since 1976; to determine the distribution of activity of subspecialty fellows; and to focus on hematology and oncology. Design: Repeated mail survey with telephone follow-up. Participants: All directors of subspecialty training programs in internal medicine in the United States. Results: The 1988-1989 census identified 7530 fellows in training, 55 more than in 1987-1988. There are 24 more first-year fellows. Reports on the activities of subspecialty fellows show that, overall, 53% of fellows' time is spent in direct patient care, 20% on basic research, 15% on patient-related research, and 12% in teaching. Conclusions: The number of internists entering subspecialty training has risen at a considerably slower rate in the last 5 years compared with the 5 years before that. The length of subspecialty training has increased significantly since 1976. There has been a shift in subspecialty choice from hematology to oncology and toward joint programs offering both subspecialties.
Meiotic nondisjunction in the mouse: methodology for genetic testing and comparison with other methods
Authors: Liane B. Russell
Journal: Environmental Health Perspectives (1979)

Since trisomies produce adverse effects relatively late in development or even postnatally, they are an important component of the array of genetic damages that might be caused by environmental agents. Whole-chromosome aneuploidy (as opposed to breakage-derived aneuploidy) might come about secondarily from crossover depression, or could follow damage to the meiotic spindle or to kinetochores. For simplicity, the event—by whichever of the mechanisms—is referred to as meiotic nondisjunction (ND). A genetic method has been devised which is based on the facts that ND involving the sex chromosomes produces mostly viable mice, and that such exceptional animals can be externally recognized by the use of appropriate markers. The method is compared with the following other ND indicators: univalent and/or chiasma frequencies at M I; number of dyads at M II; extra sex chromosomes in spermatids; karyotypes in cleavage, morula, or blastocyst metaphases; and chromosome constitution of mid-gestation embryos. Some of the cytological endpoints are found to be unreliable. Various biological variables (germ-cell stage, sex, age) are examined with a view toward maximizing the chances for detecting induced nondisjunction. While experimental evidence on this question is equivocal, a consideration of the probable ND mechanisms suggests that the early spermatocyte (in stages including the premeiotic S phase) may be a favorable test object. The numerical sex-chromosome anomaly (NSA) method is useful not only in the study of ND but also in detecting breakage-derived chromosome losses induced in females, where the dominant lethal test is not easily applicable.
442 Entecavir 10 mg is consistently superior to lamivudine at 48 weeks across multiple baseline HBV disease characteristics in lamivudine-refractory patients
Authors: E.R. Schiff, T.T. Chang, R.G. Gish, S. Hadziyannis, J. Cianciara, M. Rizzetto, G. Pastore, A. Cross, R. Hindes
Journal: Journal of Hepatology (2004)
Serial Dacryoscintigraphy Before and After Treatment with Pseudoephedrine
Authors: CHUN K. KIM, CHRISTOPHER J. PALESTRO, ROBERT W. SOLOMON, STANLEY J. GOLDSMITH
Journal: Clinical Nuclear Medicine (1989)

Radionuclide dacryoscintigraphy is an accurate physiologic method for evaluating the nasolacrimal drainage apparatus. The following case report illustrates the role of this procedure in the initial workup of epiphora, as well as its value in assessing response to therapy with pseudoephedrine.