tbuckley/cabot-search huggingface dataset:
Intramuscular Therapeutic Vaccination Targeting HPV16 Induces T Cell Responses That Localize in Mucosal Lesions
Authors: Leonel Maldonado, Jessica E. Teague, Matthew P. Morrow, Iveta Jotova, T. C. Wu, Chenguang Wang, Cindy Desmarais, Jean D. Boyer, Benjamin Tycko, Harlan S. Robins, Rachael A. Clark, Cornelia L. Trimble
Journal: Science Translational Medicine (2014)

About 25% of high-grade cervical intraepithelial neoplasias (CIN2/3) caused by human papillomavirus serotype 16 (HPV16) undergo complete spontaneous regression. However, to date, therapeutic vaccination strategies for HPV disease have yielded limited success when measured by their ability to induce robust peripheral blood T cell responses to vaccine antigen. We report marked immunologic changes in the target lesion microenvironment after intramuscular therapeutic vaccination targeting HPV16 E6/E7 antigens, in subjects with CIN2/3 who had modest detectable responses in circulating T lymphocytes. Histologic and molecular changes, including markedly (average threefold) increased intensity of CD8(+) T cell infiltrates in both the stromal and epithelial compartments, suggest an effector response to vaccination. Postvaccination cervical tissue immune infiltrates included organized tertiary lymphoid-like structures in the stroma subjacent to residual intraepithelial lesions and, unlike infiltrates in unvaccinated lesions, showed evidence of proliferation induced by recognition of cognate antigen. At a molecular level, these histologic changes in the stroma were characterized by increased expression of genes associated with immune activation (CXCR3) and effector function (Tbet and IFNβ), and were also associated with an immunologic signature in the overlying dysplastic epithelium. High-throughput T cell receptor sequencing of unmanipulated specimens identified clonal expansions in the tissue that were not readily detectable in peripheral blood. Together, these findings indicate that peripheral therapeutic vaccination to HPV antigens can induce a robust tissue-localized effector immune response, and that analyses of immune responses at sites of antigen are likely to be much more informative than analyses of cells that remain in the circulation.
WHAT WE GET FOR WHAT WE SPEND FOR MEDICAL CARE
Authors: Frank G. Dickinson
Journal: JAMA (1953)

INTRODUCTION  I have divided my paper into two different parts: first,  We  and, second,  We Get for What We Spend for Medical Care. First, consider  We Spend. This first half may seem rather stale to those of you who have digested the thick Fact Book that the commission distributed recently to the members of this panel. This Fact Book deals almost exclusively with the cost of medical care, with extreme emphasis on governmental costs. My emphasis will be on consumer expenditures. The Fact Book, however, gives nothing on  We Get for What We Spend. While not intending to criticize those who. planned and compiled this thick Fact Book, I do want to say quite frankly that I think it unfortunate to present only half the story of medical economics. In general, economists consider cost and value as two aspects of the central theme. Frankly, the
A NOVEL TECHNIQUE TO MEASURE DIASTOLIC FUNCTION USING A PROTOTYPE SPECKLE TRACKING ECHOCARDIOGRAPHY SYSTEM: RESULTS FROM THE RADIOFREQUENCY-BASED SPECKLE TRACKING ECHOCARDIOGRAPHY TO EVALUATE DIASTOLIC FUNCTION (RF-SPEED) STUDY
Authors: Theodore J. Kolias, Stanley Chetcuti, Diane Eberhart, Nicole Kline, James Hamilton
Journal: Journal of the American College of Cardiology (2012)
Transcriptional Architecture of the Primate Neocortex
Authors: Amy Bernard, Laura S. Lubbers, Keith Q. Tanis, Rui Luo, Alexei A. Podtelezhnikov, Eva M. Finney, Mollie M.E. McWhorter, Kyle Serikawa, Tracy Lemon, Rebecca Morgan, Catherine Copeland, Kimberly Smith, Vivian Cullen, Jeremy Davis-Turak, Chang-Kyu Lee, Susan M. Sunkin, Andrey P. Loboda, David M. Levine, David J. Stone, Michael J. Hawrylycz, Christopher J. Roberts, Allan R. Jones, Daniel H. Geschwind, Ed S. Lein
Journal: Neuron (2012)
Development of the pharyngeal arch system related to the pulmonary and bronchial vessels in the avian embryo. With a concept on systemic-pulmonary collateral artery formation.
Authors: M C DeRuiter, A C Gittenberger-de Groot, R E Poelmann, L VanIperen, M M Mentink
Journal: Circulation (1993)

BACKGROUND The literature is ambiguous as to the question of the developmental background of systemic-pulmonary collateral arteries. These are found in combination with various congenital heart malformations such as pulmonary atresia. From a clinical point of view, it is of interest to know whether we are dealing with the persistence of transient embryological vessels such as ventral segmental arteries or parts of pharyngeal arch arteries or with the prenatal or postnatal recruitment of the bronchial vasculature that normally supplies the lung. This study of the embryology of the extrapulmonary and intrapulmonary vasculature aims at a better understanding of the variations in origin, course, branching pattern, and histology of collateral arteries. METHODS AND RESULTS Serial sections of quail embryos ranging between stage HH11 and stage HH28 were incubated with a monoclonal antibody (alpha MB1) against endothelial cells and their precursors. Additional series of chick embryos were injected with india ink to study the lumenized vascular patterns. A splanchnic plexus consisting of endothelial cells and precursors is present around the foregut before the lung buds develop. This plexus expands and gives rise to the pharyngeal arch arteries, the ventral pharyngeal veins, the pulmonary vessels, and the bronchial vessels, including the intrapulmonary vessel network. During two subsequent periods, the splanchnic plexus is transiently connected to the systemic arteries and veins. The bronchial arteries and veins develop in the second period from these transient vessels. The expansion and extension of the splanchnic plexus to many organs during the formation of the bronchial vessels explains the varying course and branching pattern of the bronchial vasculature. CONCLUSIONS These results show that we are not dealing with two or more individual vascular systems that contribute to the developing vessels of the lungs but with one vascular plexus that normally gives rise to the pulmonary and bronchial vasculature but has the potential to give rise to other systemic-pulmonary connections.
Role of intact cardiac nerves and reflex mechanisms in desensitization to catecholamines in conscious dogs.
Authors: J Nejima, N Uemura, D E Vatner, C J Homcy, T H Hintze, S F Vatner
Journal: Journal of Clinical Investigation (1990)

To study chronic catecholamine desensitization, mini-osmotic pumps were implanted subcutaneously to deliver NE, (0.5 micrograms/kg/min) or saline over 3-4 wk in dogs instrumented with left ventricular (LV) pressure gauges and arterial and left atrial pressure catheters. An acute challenge to NE (0.4 micrograms/kg/min) in intact, conscious dogs increased LV dP/dt by 1,531 +/- 208 mmHg/s before NE pumps, and by a similar amount, 1,340 +/- 166 mmHg/s, 3-4 wk after NE pumps. In contrast, an acute challenge to isoproterenol (ISO, 0.4 micrograms/kg/min) increased LV dP/dt by 5,344 +/- 532 mmHg/s before NE pumps, and significantly less (P less than 0.05; 2,425 +/- 175 mmHg/s) after NE pumps. In the presence of ganglionic and alpha 1-adrenergic blockades, NE (0.4 micrograms/kg/min) increased LV dP/dt by 3,656 +/- 468 mmHg/s before NE pumps and significantly less (P less than 0.01; 1,459 +/- 200 mmHg/s) after NE pumps. Confirming this, an acute challenge to NE (0.4 micrograms/kg/min) in dogs with arterial baroreceptor denervation increased LV dP/dt by 3,732 +/- 896 mmHg/s before NE pumps, and significantly less (P less than 0.05, 1,725 +/- 408 mmHg/s) after NE pumps. In addition, in cardiac denervated dogs, NE (0.4 micrograms/kg/min) increased LV dP/dt by 9,901 +/- 1,404 mmHg/s before NE pumps and significantly less (P less than 0.01, 2,690 +/- 306 mmHg/s) after NE pumps. Desensitization of heart rate responses to NE challenge was also more apparent in the absence of reflex mechanisms. Thus, neural reflex mechanisms play a major role in physiological expression of cardiac desensitization to catecholamines in conscious dogs.
ON SOME POINTS IN THE PATHOLOGY, DIAGNOSIS, AND TREATMENT OF PNEUMONIA
Authors: C. H. F. Routh
Journal: BMJ (1855)

Is a former paper on Pneumonia, I alluded to some points in its diagnosis, prognosis, and the theory which recom- mended, on erroneous grounds, the treatment by blood- letting.I now come to speak of the exrperience of various modes of practice: but, before I do so, allow me to recapitulate some of the points to which I alluded in my last paper.In speakingof thepathological character of the blood,I at- tempted to prove that that fluid at first was unusually thin, from a deficiency of chlorides; secondly, that it became hype- rinosed by the increased number of the respiratory move- ments, and the greater activity of thc function of the skin, viewing this as a respiratory, organ also, and the intense heat of surface as evidence of this increased action.I alluded to this last as evidence of adynamic type; and also to the frequent occurrence of pneumonia from poisonous causes, as in typhus; from phlebitis, after injuries and operations; and by artificial poisoning of the blood.I then spoke of the large number of depressing among the known causes of its production.I then referred to the diagnosis between pneumonia and some other diseases, namely, simple pulmonary congestion, capillary bronchitis, and some forms of pleuritis; then to its prognosis, and the tendency of death by depression; and, lastly, I proved that the theory which recommended the blood-letting treatTnent was erroneous, because its moderate employment did not diminish the amount of fibrin; secondly, because, although it checked the general fever, it lengthened the convales- cence; thirdly, it did not remove the local symptoms, but, in most cases of intense pneumonia, it aggravated them; fourthly, that the type of disease was generally now more adynamic, and that pneumonia proved generally fatal in proportion as this character was more marked.The last point under this head involves the question of experience, viz., the results of the treatment by blood-lettinkg-its infuence on mortality.I purposely, therefore, refrained from entering upon its discussion on the last occasion; but its consideration necessarily opens the subject of the paper, to which I venture this evening to solicit your attention.I. Treatment by Blood-Leing.It is alleged that, by carrying out blood-letting freely, the mortality is dimin- ished.But who is there amongst us who will undertake to state what is the niormal mortality of pneumonia, affected as it is by sex, age, habits of life, seasons, seat, complication with other diseases, and treatment?Take for instance the following table : Cases.Deaths.Per cent.
493. Concentration and Purification of Lentivirus Pseudotypes Bearing Alternative Envelope Glycoproteins
Authors: Robert H. Kutner, Jakob Reiser
Journal: Molecular Therapy (2005)

Current problems that impact the use of lentiviral (LV) vectors for applications in large animals include low titers, poor purity and difficulties related to their large-scale production. A number of useful protocols are available to concentrate and purify LV vector pseudotypes bearing the traditional vesicular stomatitis virus G (VSV-G) glycoprotein. These protocols include centrifugation-based approaches, ultrafiltration, anion exchange chromatography, and size exclusion chromatography. There is an increasing demand for alternative (i.e. non-VSV-G-based) LV pseudotypes and thus there are needs for improved concentration/purification protocols for such pseudotypes. We have investigated scaleable protocols for the capture and purification of alternative LV pseudotypes based on anion exchange membrane chromatography. In one approach, HIV-1-based LV vectors pseudotyped with a lyssavirus (rabies-related) glycoprotein were generated by transient transfection. In another approach, amphotropic LV pseudotypes were generated using the STAR-A amphotropic packaging cell line. Virus-containing cell culture supernatants were subsequently captured onto chromatography membranes bearing functional quarternary (Q) ammonium groups and eluted with high salt and then desalted and further concentrated by ultrafiltration. Using this procedure, up to 87 % of the virus applied (up to 1.8 |[times]| 108 transducing units) could be recovered from a single anion exchange membrane unit with a membrane bed volume of 0.18 ml. Our results indicate that these purification procedures are useful for concentrating LV vectors bearing alternative envelope glycoproteins with a minimal loss of infectivity. We expect these approaches to facilitate the preparation of lentiviral vectors for large-scale preclinical studies. They may ultimately be applicable to generate clinical-grade LV vectors.
A CASE OF CARCINOMA OF THE NASAL PASSAGES.
Authors: J. L. GOODALE
Journal: JAMA (1900)

Mr. J. A. S., a commercial traveler, 51 years of age, was referred to me by Dr. F. E. Cheney of Boston, June 4, 1898. <h3>Previous History.</h3> —For thirty-three years the patient had had nasal polypi removed at regular and frequent intervals from the left nasal passage, by various physicians, and within the past few years also occasionally from the right side. Otherwise the health had been good. There was no evidence of syphilis. <h3>Present Illness.</h3> —Six months ago the polypi on the left side were said to have become firmer and their removal attended with more bleeding than formerly. The left eye simultaneously became painful and began to exhibit protrusion from the orbit. A progressive impairment of flesh and strength was observed. <h3>Examination.</h3> —He was well developed and fairly well nourished. The right nasal passage contained a few small polypi; the left was nearly completely filled with small and
Clinical Usefulness of Different Lipid Measures for Prediction of Coronary Heart Disease in Type 2 Diabetes
Authors: Björn Eliasson, Jan Cederholm, Katarina Eeg-Olofsson, Anne-Marie Svensson, Björn Zethelius, Soffia Gudbjörnsdottir
Journal: Diabetes Care (2011)

We assessed the association between different blood lipid measures and risk of fatal/nonfatal coronary heart disease (CHD).We conducted an observational study of patients with type 2 diabetes from the Swedish National Diabetes Register. Baseline LDL cholesterol, non-HDL cholesterol, ratio of non-HDL to HDL cholesterol (non-HDL:HDL), and ratio of triacylglycerol to HDL cholesterol (TG:HDL) was measured in 18,673 patients aged 30-70 years, followed for a mean of 4.8 years from 2003 to 2007.Hazard ratios (HRs) for CHD per 1-SD increment in lipid measures were 1.23 with non-HDL:HDL, 1.20 with non-HDL cholesterol, 1.17 with LDL cholesterol, and 1.15 with TG:HDL (all P < 0.001 when adjusted for clinical characteristics and nonlipid risk factors). The best global model fit was found with non-HDL:HDL. When patients within the lowest tertile of a lipid measure were compared with those with all lipid measures within the highest tertile, the adjusted HR for CHD was 0.62 with non-HDL:HDL <3.5 mmol/L, 0.65 with non-HDL cholesterol <3.3 mmol/L, and 0.70 with LDL cholesterol <2.5 mmol/L (all P < 0.001). The lowest tertile of LDL and non-HDL cholesterol corresponded with treatment targets according to U.S. and European guidelines. HRs for CHD were 0.52, 0.62, and 0.66 with the lowest deciles of non-HDL:HDL, non-HDL cholesterol, and LDL cholesterol ≤1.8 mmol/L (all P < 0.001). Mean TG:HDL was considerably lower in patients within the lowest tertile of non-HDL:HDL, 0.82 ± 0.47, than in those within the lowest tertile of LDL cholesterol (<2.5 mmol/L), 1.49 ± 1.03.Non-HDL:HDL had a stronger effect on CHD risk than LDL cholesterol, and low TG:HDL values were more often seen within the lowest non-HDL:HDL tertile than within the lowest LDL cholesterol tertile. LDL cholesterol was not the best predictor of CHD risk in type 2 diabetes.
Doctor of Primary Medicine
Authors: H. T. Are
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Dr. Proger's EDITORIAL proposes PMD as an academic degree to be bestowed on this special kind of physician upon graduation from a special kind of medical school. Now "MD" stands for the Latin, "medicinae doctor." This being so, whether one is in Rome or elsewhere, one feels obliged to complete Proger's designation by following classical Latin construction, "medicinae primae doctor (MPD)," which would be proper enough, but not widely understood. If it is the physician that is primary rather than his branch of medicine, one would write, "medicinae doctor primus (MDP)," or in plain English, "primary doctor of medicine (PDM)" —an unheard-of breach in the ramparts of academic heraldry. But is it possible that Dr. Proger, after all, is plumping for English by making PMD out of "primary medical doctor"? I doubt that he, or anyone, would dare. I come to the sad conclusion that the term
Cocaine Use and the Risk for Endocarditis in Intravenous Drug Users
Authors: HENRY F. CHAMBERS
Journal: Annals of Internal Medicine (1987)

Endocarditis is a relatively frequent infection in intravenous drug users. We compared features in the cases of 102 patients with those in intravenous drug users with other causes of fever to identify risk factors predictive of endocarditis. Logistic regression analysis showed cocaine use to be strongly associated with endocarditis. This special risk involving cocaine use has not been reported previously; the explanation for it may provide insight into the pathogenesis of endocarditis.
Scanning during pregnancy is often for doctors' benefit rather than parents'
Authors: B E Price
Journal: BMJ (1999)

EDITOR—Nine years ago I was expecting a baby and was excited about my first scan. Everything seemed normal until the hospital asked me to return, with my husband, because they wanted to discuss the scan. Immediately I felt alarmed and worried.

We went to see the registrar, who said that the staff had noticed that the placenta did not look normal and that it was “hydropic.” I was asked to attend Heath Hospital, Cardiff, to undergo a series …
The effect of cetirizine on sulfidoleukotriene production by blood leukocytes in children with allergic rhinitis
Authors: Ö. Kalayci, Y. Saraclar, G. Adalioglu, B. Sekerel, A. Tuncer
Journal: Allergy (1995)

Twelve children with allergic rhinitis due to monosensitivity to Dermatophagoides pteronyssinus (Dp) took part in a placebo‐controlled, double‐blind, crossover study to evaluate the effect of cetirizine, a second‐generation, nonsedating H 1 ‐blocker‐type antihistamine, on sulfidoleukotriene releasability by blood leukocytes and to determine its correlation with clinical findings and nasal challenge scores. Sulfidoleukotriene release by blood leukocytes was determined by the cellular allergen stimulation test (CAST), which measures leukotriene (LT)C 4 , LTD 4 , and LTE 4 , all in one assay. Compared to placebo, cetirizine significantly ( P ≤0.05) decreased daily symptom scores of nasal discharge, nasal itching, and sneezing, as well as the number of sneezings after nasal challenge with the antigen, without alleviating nasal obstruction ( P ≥0.05). It also suppressed both early ( P ≤0.05) and late skin reactions to intradermal tests. Although cetirizine did not influence in vitro sulfidoleukotriene production by blood leukocytes with buffer or anti‐IgE ( P ≥0.05), it substantially reduced the release of these mediators upon challenge with Dp antigen. Furthermore, there was a high correlation between the number of sneezes after challenge and the amount of sulfidoleukotriene released in nine patients ( r =0.78; P ≤0.01). It is concluded that the amount of sulfidoleukotrienes produced by blood leukocytes in vitro may reflect the nasal hyperreactivity of the patient, and that cetirizine, which is highly effective in the treatment of allergic rhinitis, owes part of its effect to inhibition of sulfidoleukotriene releasability by blood leukocytes in children.
A NEW ANAL SPECULUM
Authors: William M. Beach
Journal: JAMA (1924)

The proctologist has been hampered heretofore by the lack of a suitable instrument to expose the anal canal painlessly for deliberate inspection. Many instruments have been devised for the purpose, but all give an imperfect view of the structures, besides producing much discomfort to the conscious patient. The ordinary bivalve speculum may be all that is desired in the anesthetized patient, but even in that event, the instrument must be held by the operator or his assistant during the inspection and treatment. The new instrument has the triple virtues that (<i>a</i>) introduction is painless; (<i>b</i>) sufficient spread of the exposed anal wall is allowed for careful inspection of crypts, submucous tracts, etc., and (<i>c</i>) it is self-retaining. An electric lamp may be attached near the distal end, but good daylight or projected artificial light will give sufficient illumination. In form and size, the reposed instrument is fashioned after a No.
Immunoproteomic Analysis of Potentially Severe Non-Graft-Versus-Host Disease Hepatitis After Allogenic Bone Marrow Transplantation
Authors: Elvire Beleoken, Rodolphe Sobesky, Jean-Pierre Le Caer, François Le Naour, Mylène Sebagh, Nicolas Moniaux, Bruno Roche, Mohammad Zahid Mustafa, Catherine Guettier, Catherine Johanet, Didier Samuel, Jean-Henri Bouhris, Jean-Charles Duclos-Vallee, Eric Ballot
Journal: Hepatology (2012)

The development of potentially severe non-graft-versus-host disease (GVHD) hepatitis resembling autoimmune hepatitis (AIH) has been reported after bone marrow transplantation (BMT). The aim of this study was to better characterize this form of hepatitis, particularly through the identification of autoantigens recognized by patient sera. Five patients who received an allogeneic BMT for the treatment of hematological diseases developed liver dysfunction with histological features suggestive of AIH. Before and during the onset of hepatic dysfunction, sera were tested on immunoblottings performed with cytosolic, microsomal, mitochondrial, and nuclear proteins from rat liver homogenate and resolved by two-dimensional electrophoresis. Antigenic targets were identified by mass spectrometry. During the year that followed BMT, all patients presented with GVHD. Acute hepatitis then occurred after the withdrawal, or during the tapering, of immunosuppressive therapy. At that time, no patients had a history of liver toxic drug absorption, patent viral infection, or any histopathological findings consistent with GVHD. Immunoreactive spots stained by sera collected at the time of hepatic dysfunction were more numerous and more intensely expressed than those stained by sera collected before. Considerable patient-dependent pattern heterogeneity was observed. Among the 259 spots stained exclusively by sera collected at the time of hepatitis, a total of 240 spots were identified, corresponding to 103 different proteins. Twelve of them were recognized by sera from 3 patients. Conclusions: This is the first immunological description of potentially severe non-GVHD hepatitis occurring after BMT, determined using a proteomic approach and enabling a discussion of the mechanisms that transform an alloimmune reaction into an autoimmune response. Any decision to withdraw immunosuppression after allogeneic BMT should be made with caution.