tbuckley/cabot-search huggingface dataset:
T cell clones specific for an amphipathic alpha-helical region of sperm whale myoglobin show differing fine specificities for synthetic peptides. A multiview/single structure interpretation of immunodominance.
Authors: K B Cease, I Berkower, J York-Jolley, J A Berzofsky
Journal: The Journal of Experimental Medicine (1986)

The T cell response to sperm whale myoglobin in the H-2d haplotype has been shown to be largely focused on a limited region around glutamic acid 109 recognized in association with I-Ad. T cell clones 9.27 and 1.2 have been previously (4, 5) shown to reflect this specificity and MHC restriction. In this study we have used a panel of synthetic peptides from the region 102-118 of myoglobin to characterize the specificities of these representative clones. The segment from 106-118 was found to represent a consensus region for recognition by both clones. However, we saw significant differences between clones in the hierarchy of responsiveness to peptides within the panel. In as much as the peptide and the I-Ad molecule remain constant, these differences derive from differences in how each T cell receptor interacts with the antigen. This peptide segment is an amphipathic alpha helix in native myoglobin, meaning that one side is hydrophobic and the other hydrophilic. It is one of the prototype cases that led us to find that amphipathic helices constitute the majority of immunodominant sites recognized by helper T cells (1). It is likely that the peptide will refold into an amphipathic helix stabilized by the interface at the surface of the presenting cell. When such secondary conformation is considered, these data are consistent with a model of multiple T cell specificities arising from multiple views of a single antigen conformation at a single Ia-binding site and do not require postulation of multiple conformations or binding sites. Additionally, the finding of distinct specificities suggests that the immunodominance of this site depends not on the dominance of a single clone, but on the focusing of a polyclonal response on a single region of the molecule in association with I-Ad. The immunodominance of this particular region of the protein may thus depend on intrinsic features of the site, such as potential to form an amphipathic helix, as well as extrinsic factors such as binding properties of the I-A molecule.
Money motives, moral philosophy, and biological explanations
Authors: Adrian J. Walsh
Journal: Behavioral and Brain Sciences (2006)

Lea &amp; Webley (L&amp;W) provide two alternative biological accounts of human monetary motivations, the Tool Theory and the Drug Theory. They argue that both are required for an adequate explanation. I explore the applicability of these models to philosophical discussions of how we might justify such motivations. I argue their approach is not entirely satisfactory for normative questions, since it precludes the possibility of rational non-instrumental attitudes towards money.
Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability
Authors: Ankush Choudhary, Avtar C. Rana, Geeta Aggarwal, Virender Kumar, Foziyah Zakir
Journal: Acta Pharmaceutica Sinica B (2012)

Atorvastatin has low aqueous solubility resulting in low oral bioavailability (12%) and thus presents a challenge in formulating a suitable dosage form. To improve the aqueous solubility, a solid dispersion formulation of atorvastatin was prepared by lyophilization utilising skimmed milk as a carrier. Six different formulations were prepared with varying ratios of drug and carrier and the corresponding physical mixtures were also prepared. The formation of a solid dispersion formulation was confirmed by differential scanning calorimetry and X-ray diffraction studies. The optimum drug-to-carrier ratio of 1:9 enhanced solubility nearly 33-fold as compared to pure drug. In vitro drug release studies exhibited a cumulative release of 83.69% as compared to 22.7% for the pure drug. Additionally, scanning electron microscopy studies suggested the conversion of crystalline atorvastatin to an amorphous form. In a Triton-induced hyperlipidemia model, a 3-fold increase in the lipid lowering potential was obtained with the reformulated drug as compared to pure drug. These results suggest that solid dispersion of atorvastatin using skimmed milk as carrier is a promising approach for oral delivery of atorvastatin.
Incremental Health Care Reform
Authors: Troyen A. Brennan
Journal: JAMA (2009)

FOR THE 15 YEARS SINCE THE LAST EFFORTS AT MAJOR federal health reform receded, advocates have waited for the right moment to push again. That time appears be now, as the Obama administration seems committed to health reform. Further, consensus seems to be emerging among health reform advocates on the structure of reform beyond extension of the State Children’s Health Insurance Program (SCHIP). Momentum is gathering around the combination of 2 reforms: making Medicare available to all citizens and strengthening public oversight of the small-group and individual insurance markets through a Massachusetts-style “connector.” The 2 together would create more substantial governmental oversight and control of health care than ever before, but this would occur in what appears to be an incremental fashion and market competition could ostensibly be preserved. As a result, the proposal may be more politically palatable than previous reform efforts. In this Commentary, we review this approach and the factors that give it political momentum.
The European LABDEL project and its relevance to the prevention and treatment of allergies
Authors: C. Daniel, A. Repa, A. Mercenier, U. Wiedermann, J. Wells
Journal: Allergy (2007)

In March 2001, the European Commission funded a 3‐year project (contract no. QLK3‐CT‐2000‐00340) under the fifth Framework Programme to develop and test prototype products based on the oral delivery of vaccine and therapeutic agents using harmless lactic acid bacteria (LAB). The project, best known under its acronym LABDEL (for LAB delivery) also included research on LAB fermentation and technological innovations aimed at enhancing the efficiency of LAB delivery systems ( 1 ). One of the key scientific objectives was to investigate the possibility to prevent or treat a type I allergic disease using mucosal administration of LAB expressing the pollen allergen Bet v 1. The aim of this paper was to describe the background of the project with reference to a limited selection of articles and recent reviews as well as the results and major conclusions arising from this part of the project.
Changes in Breath Trihalomethane Levels Resulting from Household Water-Use Activities
Authors: Sydney M. Gordon, Marielle C. Brinkman, David L. Ashley, Benjamin C. Blount, Christopher Lyu, John Masters, Philip C. Singer
Journal: Environmental Health Perspectives (2005)

Common household water-use activities such as showering, bathing, drinking, and washing clothes or dishes are potentially important contributors to individual exposure to trihalomethanes (THMs), the major class of disinfection by-products of water treated with chlorine. Previous studies have focused on showering or bathing activities. In this study, we selected 12 common water-use activities and determined which may lead to the greatest THM exposures and result in the greatest increase in the internal dose. Seven subjects performed the various water-use activities in two residences served by water utilities with relatively high and moderate total THM levels. To maintain a consistent exposure environment, the activities, exposure times, air exchange rates, water flows, water temperatures, and extraneous THM emissions to the indoor air were carefully controlled. Water, indoor air, blood, and exhaled-breath samples were collected during each exposure session for each activity, in accordance with a strict, well-defined protocol. Although showering (for 10 min) and bathing (for 14 min), as well as machine washing of clothes and opening mechanical dishwashers at the end of the cycle, resulted in substantial increases in indoor air chloroform concentrations, only showering and bathing caused significant increases in the breath chloroform levels. In the case of bromodichloromethane (BDCM), only bathing yielded a significantly higher air level in relation to the preexposure concentration. For chloroform from showering, strong correlations were observed for indoor air and exhaled breath, blood and exhaled breath, indoor air and blood, and tap water and blood. Only water and breath, and blood and breath were significantly associated for chloroform from bathing. For BDCM, significant correlations were obtained for blood and air, and blood and water from showering. Neither dibromochloromethane nor bromoform gave measurable breath concentrations for any of the activities investigated because of their much lower tap-water concentrations. Future studies will address the effects that changes in these common water-use activities may have on exposure.
The acute hemodynamic effects of intravenous verapamil in coronary artery disease. Assessment by equilibrium-gated radionuclide ventriculography.
Authors: H O Klein, R Ninio, V Oren, R Lang, P Sareli, E DiSegni, D David, J Guerrero, E Kaplinsky
Journal: Circulation (1983)

The acute hemodynamic effects of an i.v. bolus of verapamil, 0.1 mg/kg or 0.06-0.075 mg/kg, were examined by serial radionuclide studies in 46 patients with coronary artery disease. In 20 patients with ejection fractions (EFs) greater than 35% (group 1A), verapamil, 0.1 mg/kg given over 1-11/2 minutes, had a biphasic effect: first, a transient decrease in EF accompanied by increased left ventricular (LV) volumes and cardiac output equivalents; then, an overshoot of EF to values above control, accompanied by a decrease in peripheral vascular resistance and a drastic decrease in LV volumes, while cardiac output equivalent remained slightly elevated. In eight patients with EFs less than 35% (group 1B), only the first effect on EF was noted. In 10 patients with EFs greater than 35% (group 2), verapamil, 0.06-0.075 mg/kg, exerted qualitatively similar but milder effects on hemodynamic function. Finally, verapamil, 0.1 mg/kg given more slowly, over 2-21/2 minutes, produced no significant changes in EF or LV volumes in another eight patients (group 3). The acute effects of verapamil are thus both time-related and dose-dependent. They are also related to the baseline functional reserve of the left ventricle. This study documents that verapamil exerts a depressant effect on LV function. However, the transient nature of this depression and the quick recovery to normal or above-normal values indicate that verapamil, in the doses used in this study, is safe to use intravenously in patients with coronary artery disease.
Exercise Tests After Myocardial Infarction
Authors: ASHOK K. AGARWAL
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 February 1982Exercise Tests After Myocardial InfarctionASHOK K. AGARWAL, M.D.ASHOK K. AGARWAL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-2-250_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I write to point out that there are contradictory statements in the editorial by Stang and Lewis (1).1. Extensive experience of exercising patients between 1 and 3 weeks after infarction has already shown the apparent safety of this technique.2. Not to do an exercise test before discharge is, in a way, to ask the patient to do the treadmill test at home.3. Early exercise testing after infarction probably should remain a technique for tertiary care centers and not be used in every hospital giving coronary care.Why if a modified stress test after infarction...Reference1. STANGLEWIS JR. Early exercise tests after myocardial infarction. Ann Intern Med. 1981;94:814-5. Editorial. LinkGoogle Scholar1. FISHMAN I. Exercise tests after myocardial infarction. Ann Intern Med. 1981;95:390. Letter. LinkGoogle Scholar2. HOROWITZ W. Exercise tests after myocardial infarction. Ann Intern Med. 1981;95:390-1. Letter. LinkGoogle Scholar3. MAUTNER R. Staging after myocardial infarction. Ann Intern Med. 1981;95:514. Letter. LinkGoogle Scholar4. STANGLEWIS JR. Early exercise tests after myocardial infarction. Ann Intern Med. 1981;94:814-5. Editorial. LinkGoogle Scholar5. SCHUSTERBULKLEY EB. Early post-infarction angina. Ischemia at a distance and ischemia in the infarct zone. N Engl J Med. 1981;305:1101-5. CrossrefMedlineGoogle Scholar6. PODRIDGRABOYSLOWN PTB. Prognosis of medically treated patients with coronary artery disease with profound ST-segment depression during exercise testing. N Engl J Med. 1981;305:1111-6. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Medical Center Marion, IL 62959 Southern Illinois University School of Medicine Carbondale, IL 62901 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1982Volume 96, Issue 2Page: 250-250KeywordsExerciseInfarctionMyocardial infarctionSafety Issue Published: 1 February 1982 PDF DownloadLoading ...
Parents in the recovery room: survey of parental and staff attitudes
Authors: P A Hall, J F Payne, C G Stack, M A Stokes
Journal: BMJ (1995)

It is unusual in British hospitals for parents to be with their child while recovering from anaesthesia, although their presence during induction of anaesthesia is now common. Parents are encouraged to be with their child in other clinical areas,1 and American experience suggests many parents value being present in the recovery room.2 Before introducing this practice in our hospital we sought to determine the attitudes of parents and staff to parental presence during recovery from anaesthesia.

We invited the parents of 150 consecutive children presenting for elective surgery to come to the recovery room as their child emerged from anaesthesia. Recovery staff decided when to call the parent, with the guidelines that the child should be awakening, maintaining …
Emotions and Emotional Disorders; a Neurophysiological Study
Authors: Louis D. Boshes
Journal: JAMA (1963)

This comprehensive volume represents the fruit of a lifetime of personal research and study in the field of emotions and emotional disturbances. Both student and physician will welcome this complete exposition of basic studies correlated clinically, and directed to the vast literature on psychosomatic medicine. There are seven major areas in this authoritative treatise. The first surveys basic features of nervous system integration and describes the role of various areas in the central nervous system related to the neural substrate of emotion. Next, foundations and applications of hypothalamic tests in neuropsychiatric patients are presented. Then the authors describe that basic unity which exists between physiological and psychological processes. Part 4 follows quite logically with a discussion of sensory deprivation, stress, and emotion as encountered in the experimental neuroses. There is next presented continued emphasis on various alterations due to hypothalamic imbalance, hypertension, peptic ulcer, vagotonia and sympathotonia, nausea and fever,
Sleep Apnea in Acromegaly
Authors: Ronald R. Grunstein, Kian Y. Ho, Colin E. Sullivan
Journal: Annals of Internal Medicine (1991)

▪ Objective: To provide information on the nature, prevalence, and severity of sleep apnea in patients with acromegaly. ▪ Design: Consecutive case series. ▪ Setting: Tertiary referral hospital. ▪ Patients: Fifty-three patients with acromegaly were consecutively referred: 33 patients were referred because of clinical suspicion of sleep apnea and 20 patients were referred without suspected apnea. ▪ Measurements: Sleep studies as well as growth hormone and insulin-like growth factor 1 (IGF-1) measurements were done. ▪ Main Results: Thirty-one patients (93%; 95% Cl, 85% to 100%) referred because of suspicion of sleep apnea had sleep apnea compared with 12 patients (60%; Cl, 37% to 83%) referred without suspected sleep apnea. Patients with sleep apnea did not have biochemical evidence of increased disease activity (random growth hormone, 12.7 ± 4.4 μg/L; mean growth hormone at 24-hour sampling, 10.8 ± 8.4 μg/L; IGF-1, 90.0 ± 7.5 nmol/L) compared with patients without sleep apnea (random growth hormone, 14.2 ± 4.9 μg/L, P > 0.2; mean growth hormone, 12.4 ± 3.5 μg/L, P > 0.2; IGF-1, 90.0 ± 10.0 nmol/L, P > 0.2). Central sleep apnea was the predominant type of apnea in 33% (Cl, 18% to 47%) of patients and was associated with higher random growth hormone and IGF-1 levels than was obstructive apnea (random growth hormone, 23.4 ± 3.9 compared with 8.8 ± 3.1 μg/L, P < 0.001; IGF-1, 126 ± 17.5 compared with 72.5 ± 7.5 nmol/L, P < 0.01). ▪ Conclusions: Sleep apnea is common in acromegaly. The rate of central sleep apnea was unexpectedly high in patients with acromegaly, and biochemical evidence of increased disease activity was associated with the presence of central apnea rather than with the degree of sleep apnea. Altered respiratory control is a possible mechanism producing sleep apnea in acromegaly.
Surveillance for Endometrial Cancer in Women Receiving Tamoxifen
Authors: Elizabeth J. Suh-Burgmann, Annekathryn Goodman
Journal: Annals of Internal Medicine (1999)

Recent studies showing a protective effect of tamoxifen in women at high risk for breast cancer have expanded the indications of the drug. While acting as an estrogen antagonist in the breast, tamoxifen can have estrogenic effects on the endometrium; consensus opinion is that tamoxifen increases the risk for endometrial cancer. Because an increasing number of women are taking tamoxifen, a strategy for gynecologic surveillance is needed. Studies examining the relation between risk for endometrial cancer and tamoxifen use have conflicting results. However, because of an overall interpretation that tamoxifen use slightly increases risk for endometrial cancer, some researchers advocate routine ultrasonography and endometrial biopsy for screening asymptomatic women receiving tamoxifen. This paper reviews the literature on endometrial cancer in women taking tamoxifen and the usefulness of various screening methods in this setting. Risk factors and screening criteria for endometrial cancer in the general population are discussed, and a strategy for surveillance of women taking tamoxifen is proposed. Patients should be screened for signs or symptoms of endometrial abnormality before taking tamoxifen. This evaluation, which should include a careful history, pelvic examination, and Papanicolaou smear, should be repeated annually while the patient is receiving tamoxifen. Although transvaginal ultrasonography is not recommended for routine screening, it is indicated if an adequate pelvic examination cannot be performed or if additional risk factors are present. The likelihood of abnormality is greater for patients who have abnormal bleeding, discharge, abnormal glandular cells on Papanicolaou smear, or an endometrial measurement on ultrasonography of more than 8 mm; these findings should prompt an aggressive evaluation of the endometrium.
Abstract 1564: Investigating the interaction of tumor xenografts with their microenvironment by combining human- and mouse- specific assays with high throughput RT-qPCR
Authors: Matthew Farren, Susie Weston, Helen Brown, Steve Powell, Robert Shaw, Neil R. Smith, Susan Lovick, Susan Ashton, Stephen R. Wedge, Simon T. Barry
Journal: Cancer Research (2011)

Abstract Tumour growth is governed by the interaction with its microenvironment through pathways that regulate tumour cell function, angiogenesis, and recruitment of associated stromal cells and immune infiltrate. These complicated biological networks can be studied in tumour xenografts using a combination of gene expression, protein and histological analysis. The majority of gene expression studies either probe expression of specific transcripts by RT-qPCR, or use broad Affymetrix microarrays to examine 1000s of genes. RT-PCR experiments may be too focussed studying the interaction of a small number of pathways, while Affymetrix is often not sensitive enough to detect low abundance transcripts, or is limited by species specificity of the probe sets. For example studying tumour stromal and endothelial cells can be challenging because these cells comprise only a small proportion of the tumour. In this study we have used high throughput RT-qPCR to specifically analyse 180 human and mouse genes (or orthologues) thought to regulate key stromal/tumour interactions in a broad xenograft panel. This approach enabled us to determine the expression patterns of potential angiogenic, migratory and survival drives of a diverse range of tumour xenograft models. Across the xenograft panel these genes distinguished tumours with an Epithelial and Mesenchymal phenotype. Interestingly we find that the transcript profile of the supporting stroma (all murine transcripts) is similar between models and key genes cluster with physiological characteristics such vessel, stromal or inflammatory phenotypes. We also used this approach to assess pharmacodynamic changes in gene expression in the tumour and host compartments in response to a VEGF signalling inhibitor. Surprisingly there was little modulation in the expression of genes in the tumour cell compartment. However, there was a clear down regulation of transcripts corresponding to endothelial cells with a concomitant reduction in the tumour vasculature. This approach has enabled us to gain insight into pre-clinical models and the response to a host targetted therapy. The data provides information that enhances understanding that can be derived using histological analysis and standard protein expression. 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 1564. doi:10.1158/1538-7445.AM2011-1564
Genome.gov Launched
Authors: Brian Vastag
Journal: JAMA (2002)

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