tbuckley/cabot-search huggingface dataset:
The Musculoskeletal Manifestations of Systemic Lupus Erythematosus
Authors: Murray Silver
Journal: JAMA (1961)

The onset of systemic lupus erythematosus (SLE) is often marked by seemingly innocent musculoskeletal symptoms, and these may dominate its early course. Unless they are recognized, patients may go on for a long time with some rheumatic diagnosis until an acute febrile episode or visceral or cutaneous symptoms afford clues to the correct diagnosis. In the course of 7 years, 23 cases of SLE have been found among the patients attending the rheumatology service of a hospital for joint diseases. The musculoskeletal symptoms varied from patient to patient and from time to time, and resembled a variety of other rheumatic states. Two important diagnostic clues are the frequent remissions and exacerbations with few or no residuals, and the discrepancy between severe rheumatic symptoms and inconspicuous physical and roentgenographic changes.
SOME SOCIAL AND MEDICAL INSTITUTIONS OF HUNGARY
Authors: T. Oliver
Journal: BMJ (1914)

SOM[E SOCIAL AND MIEDICAL, INSTITUTsIONS | potatoes anld bread, with pastry or pudding.There are SOE/OCA AD EICL SITTIN in the basement clean enamelled bath cubicles screened OF HUNGARY.[off by curtains, for which a ch1arge of 2d. is mnade, including the use of soap and towels.There is another
Prorenin, Renin, Angiotensinogen, and Angiotensin-Converting Enzyme in Normal and Failing Human Hearts
Authors: A. H. Jan Danser, Catharina A. M. van Kesteren, Willem A. Bax, Monique Tavenier, Frans H. M. Derkx, Pramod R. Saxena, Maarten A. D. H. Schalekamp
Journal: Circulation (1997)

A local renin-angiotensin system in the heart is often invoked to explain the beneficial effects of ACE inhibitors in heart failure. The heart, however, produces little or no renin under normal conditions.We compared the cardiac tissue levels of renin-angiotensin system components in 10 potential heart donors who died of noncardiac disorders and 10 subjects with dilated cardiomyopathy (DCM) who underwent cardiac transplantation. Cardiac levels of renin and prorenin in DCM patients were higher than in the donors. The cardiac and plasma levels of renin in DCM were positively correlated, and extrapolation of the regression line to normal plasma levels yielded a tissue level close to that measured in the donor hearts. The cardiac tissue-to-plasma concentration (T/P) ratios for renin and prorenin were threefold the ratio for albumin, which indicates that the tissue levels were too high to be accounted for by admixture with blood and diffusion into the interstitial fluid. Cell membranes from porcine cardiac tissue bound porcine renin with high affinity. The T/P ratio for ACE, which is membrane bound, was fivefold the ratio for albumin. Cardiac angiotensinogen was lower in DCM patients than in the donors, and its T/P ratio was half that for albumin, which is compatible with substrate consumption by cardiac renin.These data in patients with heart failure support the concept of local angiotensin production in the heart by renin that is taken up from the circulation. Membrane binding may be part of the uptake process.
Unsuccessful Attempt to Induce Transformation by Cerebrospinal Fluid in Cultured Lymphocytes from Patients with Multiple Sclerosis
Authors: Jacob A. Brody, Martha M. Harlem, John F. Kurtzke, Lon R. White
Journal: New England Journal of Medicine (1968)

RECENTLY, Fowler et al.1 reported that lymphocytes from patients with multiple sclerosis when cultured in vitro in the presence of cerebrospinal fluid underwent blastlike transformation. The lymphocyte response was similar to that observed in known cases of delayed hypersensitivity as in tuberculin-positive persons whose cells are cultured in the presence of tuberculin.2 Transformation occurred regardless of the stage of the disease and in the presence of cerebrospinal fluid from subjects not suffering from multiple sclerosis. The authors suggested that, in the absence of any universally accepted diagnostic test for multiple sclerosis, lymphocyte transformation may prove the most reliable laboratory procedure . . .
Targeting the RNA Splicing Machinery as a Novel Treatment Strategy for Pancreatic Carcinoma
Authors: Gregory M. Hayes, Patricia E. Carrigan, Alison M. Beck, Laurence J. Miller
Journal: Cancer Research (2006)

Abstract Aberrant patterns of pre-mRNA splicing have been established for many human malignancies, yet the mechanisms responsible for these tumor-specific changes remain undefined and represent a promising area for therapeutic intervention. Using immunohistochemistry, we have localized the expression of a central splicing regulator, serine-arginine protein kinase 1 (SRPK1), to the ductular epithelial cells within human pancreas and have further shown its increased expression in tumors of the pancreas, breast, and colon. Small interfering RNA–mediated down-regulation of SRPK1 in pancreatic tumor cell lines resulted in a dose-dependent decrease in proliferative capacity and increase in apoptotic potential. Coordinately, the disruption of SRPK1 expression resulted in enhanced sensitivity of tumor cells to killing by gemcitabine and/or cisplatin. A dose-dependent reduction in the phosphorylation status of specific SR proteins was detected following the down-regulation of SRPK1 and is likely responsible for the observed alterations in expression of proteins associated with apoptosis and multidrug resistance. These data support SRPK1 as a new, potential target for the treatment of pancreatic ductular cancer that at present remains largely unresponsive to conventional therapies. Furthermore, these results support the development of innovative therapies that target not only specific splice variants arising during tumorigenesis but also the splice regulatory machinery that itself may be abnormal in malignant cells. (Cancer Res 2006; 66(7): 3819-27)
Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ
Authors: Stephanie L. Constant, Jennifer L. Brogdon, Damani A. Piggott, Christina A. Herrick, Irene Visintin, Nancy H. Ruddle, Kim Bottomly
Journal: Journal of Clinical Investigation (2002)

Antigen exposure via airway epithelia is often associated with a failure to prime or with the preferential priming of Th2 cells. We previously reported that the intranasal delivery of a Th1-inducing antigen promoted Th2-dominated responses, rather than the expected Th1 responses. Thus, we proposed that when pulmonary T cell priming is induced, the lung microenvironment might intrinsically favor the generation of Th2 types of responses. To establish a potential mechanism for such preferential priming, we examined the initial interactions between antigens and resident antigen-presenting cells (APCs) within the lung. We show that intranasally delivered antigens are preferentially taken up and can be presented to antigen-specific T cells by a resident population of CD11cbright APCs. Most of these antigen-loaded APCs remained within lung tissues, and migration into secondary lymphoid organs was not crucial for T cell priming to occur within the pulmonary tract. Furthermore, these pulmonary APCs demonstrated a marked expression of IL-6 and IL-10 within hours of antigen uptake, suggesting that resident tissue APCs have the capacity to promote Th2 T cell differentiation in situ.
Immediate and long term outcome of percutaneous mitral balloon valvotomy in patients with mitral stenosis and atrial fibrillation
Authors: M.N. Leon, L. Harrell, N.A. Mahdi, H. Simosa, I. Inglessis, A. Pathan, J. Lopez, M. Mikulic, P.R. Moreno, I.F. Palacios
Journal: Journal of the American College of Cardiology (1998)
AN INTRODUCTION TO THE DISCUSSION UPON "BLOOD-SERUM THERAPEUTICS."
Authors: HAROLD C. ERNST
Journal: JAMA (1896)

Probably the most radical change in the ideas of the causation of disease that has ever occurred has taken place during the last thirty years, its final outcome being the subject of the discussion before this meeting to-day. The steps leading up to the position at present occupied have been taken only after many wanderings and painful experiences, but as a result we seem to have reached a rational standpoint from which further progress may be made. The basis of blood-serum therapeutics is the idea of<i>immunity</i>, and the procedure is the result of the investigations made to determine how immunity occurs. It had been known for a long time that after attacks of certain diseases, there was a period during which a second attack of this same disease did not occur. This was, and is, known as<i>acquired immunity</i>to the disease in question. Certain races of animals are
STUDIES UPON THE NASAL SECRETIONS. I. THE CELLULAR CONTENT OF THE NASAL SECRETIONS IN ACUTE DISEASE OF THE RESPIRATORY TRACT
Authors: Perrin H. Long, Eleanor A. Bliss, Harriet M. Carpenter
Journal: Journal of Clinical Investigation (1933)

Although common colds are probably the most frequent ailments from which we suffer, very few studies have been made upon the changes that take place in the nasal mucous membranes during acute upper respiratory infections.In 1885 MacKenzie (1) first described the histo- logical appearance of the nasal mucous membranes during acute coryza.He found an intense engorgement of the cavernous tissue which was especially well marked over the lower halves of the middle and posterior portions of the inferior turbinates with rupture of the vessels.Along the inner walls of the dilated spaces were congregations of lymphoid cells and in some of them collections of fibrinous exudate.A moderate cellular infiltration was present below the basement membrane.Forty-five years after this report, Hilding (2) published his observa- tions upon the histopathology of the nasal mucous membranes in "colds."He found that "the pathologic process is that of a mucous membrane inflammation showing rather marked tissue changes, including the loss of many of the surface cells and a proliferative reaction in the submucosa.The epithelium is regenerated and repaired by the growth and multiplica- tion of the stellate cells normally found deep in the epithelium."While studying the nasal secretions, Hilding noted that the cellular content changed rapidly.Early in colds the secretion was watery and contained few cells.Ciliated epithelial cells appeared during the first twenty-four hours and became more numerous by the second day.The deeper epithelial cells, polyblasts and polymorphonuclear cells appeared in the secretions on the second day and rapidly became numerous.Within a few days the polymorphonuclears made up most of the cellular content of the secretions.Hilding did not believe that the cellular content of the secretions or the pathological picture in the nasal mucous membranes was related to any one causal agent in colds, but interpreted the observed changes as a response to any one of or a combination of etiological factors.D. and R. Thomson (3) have briefly described nasal secretions from cases of acute watery catarrh.Their observations are of interest chiefly
THE ACUTE INFLAMMATORY REACTION IN THE RABBIT EAR CHAMBER WITH PARTICULAR REFERENCE TO THE PHENOMENON OF LEUKOCYTIC MIGRATION
Authors: W. J. Cliff
Journal: The Journal of Experimental Medicine (1966)

Responses to injections of various materials into rabbit ear chambers were studied by in vivo microscopy. The acute inflammatory responses provoked by injections of antibody-antigen complexes were both quantitatively and qualitatively different from the responses obtained after injections of either homologous sera or the antigens alone. The sticking of leukocytes to endothelium during these responses occurred only in the venules draining the injection sites and was frequently present only on the sides of the venules towards the injection sites. An explanation of this finding was proposed in terms of absorption by the minute vessels related to the injection sites of postulated mediator(s) with specific activity on venular endothelium. Analysis of the rates and direction of movement of leukocytes during the reactions produced by the antibody-antigen complexes was performed with the aid of time-lapse cinemicroscopy. The leukocytes that were sticking to the venular endothelium frequently exhibited amoeboid locomotion within the vessels. Twice as many of these cells moved against the direction of blood flow as with it. This finding was discussed and an explanation proposed. A method for detecting a drift in the overall population of emigrated leukocytes within the inflamed tissue was described and revealed that four times as many amoeboid cells moved away from the injection sites as towards them. This result was discussed in the light of the in vitro chemotactic properties of antibody-antigen complexes demonstrated for rabbit leukocytes. An alternative explanation was proposed in terms of variation in the population density of these cells and their random movements and collisions. The rates of amoeboid movement of leukocytes during the acute inflammatory reactions produced by antibody-antigen complexes were similar to the rates found during turpentine inflammation and were compared to other published values.
Risk factors for lung cancer in patients with scleroderma: a nested case-control study
Authors: E. K Pontifex, C. L Hill, P. Roberts-Thomson
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To study potential risk factors for the development of lung cancer in patients with scleroderma and explore the chronological relationship between onset of scleroderma symptoms and subtypes of lung cancer. <b>Method:</b> Linkage of two population-based registers to identify lung cancer cases and gender-matched controls with scleroderma, followed by retrospective case note review for clinical details. <b>Results:</b> Patients with scleroderma who smoke are seven times more likely to develop lung cancer than non-smokers (p = 0.008). Smokers with scleroderma and cancer smoke more than smokers with scleroderma without cancer (p = 0.019). Pulmonary fibrosis and anti-topoisomerase antibody do not increase the risk of lung cancer. Peripheral lung tumours occur earlier after the onset of scleroderma symptoms than bronchogenic tumours (p = 0.05). <b>Conclusions:</b> Smokers with scleroderma should be monitored for the presence of lung cancer and counselled to quit smoking. The earlier development of peripheral lung tumours is not consistent, with pulmonary fibrosis being an aetiological factor.
Nurse refuses "criminal" force feeding of Guantanamo detainees
Authors: J. Lenzer
Journal: BMJ (2014)

A US navy officer and nurse has been reported as refusing to participate in force feeding detainees at Guantanamo Bay Naval Base.

Cori Crider, an attorney with Reprieve, a London based legal defense group, said that her client, the Guantanamo detainee Abu Wa’el Dhiab, told her that a nurse who at first took part in the force feedings was so upset with the process that he said he would no longer participate in what he called a “criminal act.”

The World Medical Association …
Abstract 5519: Investigation of the cellular mechanisms of action of maximiscin, a novel natural product with selective cytotoxic activity against a triple negative breast cancer molecular subtype
Authors: Andrew J. Robles, Lin Du, Jarrod B. King, Robert H. Cichewicz, Susan L. Mooberry
Journal: Cancer Research (2014)

Abstract Natural products have historically been an excellent resource for new pharmaceuticals, particularly anticancer agents. Fungi are a remarkable source of novel secondary metabolites that have never been evaluated for their therapeutic potential. However, a vast majority of fungal species found in diverse environments are inaccessible to research scientists. We recently isolated and identified the natural product maximiscin from a Tolypocladium sp. isolate obtained through a crowdsourcing initiative. This compound showed in vitro cytotoxic potency against multiple cancer cell lines in the NCI-60 in vitro screening panel and in vivo antitumor efficacy against a UACC-62 melanoma xenograft model. MDA-MB-468, a triple negative breast cancer (TNBC) cell line of the basal-like 1 (BL1) subtype, was found to be particularly sensitive to the cytotoxic effects of maximiscin compared to several other TNBC cell lines. This finding suggests maximiscin modulates a cellular signaling pathway that specifically drives the BL1 subtype of TNBC. In this study we investigated the cellular mechanisms of action of maximiscin using cell biological and biochemical approaches. The effects of maximiscin on cell cycle distribution were evaluated and maximiscin reduced the fraction of cells in the S and G2/M phases of the cell cycle, and began to induce apoptosis within 8 h. Intracellular signaling through multiple pathways was evaluated by immunoblotting, providing an indication of potential mechanisms of action. Maximiscin also circumvented P-glycoprotein-mediated multidrug resistance. These studies suggest maximiscin may have therapeutic potential for the treatment of BL1 TNBC, especially in cases where P-glycoprotein-mediated multidrug resistance has developed. Studies are ongoing to further characterize the cellular and antitumor effects of maximiscin in BL1 models. Citation Format: Andrew J. Robles, Lin Du, Jarrod B. King, Robert H. Cichewicz, Susan L. Mooberry. Investigation of the cellular mechanisms of action of maximiscin, a novel natural product with selective cytotoxic activity against a triple negative breast cancer molecular subtype. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5519. doi:10.1158/1538-7445.AM2014-5519
Enhanced intestinal transepithelial antigen transport in allergic rats is mediated by IgE and CD23 (FcεRII)
Authors: Ping-Chang Yang, M. Cecilia Berin, Linda C.H. Yu, Daniel H. Conrad, Mary H. Perdue
Journal: Journal of Clinical Investigation (2000)

We previously reported that active sensitization of rats resulted in the appearance of a unique system for rapid and specific antigen uptake across intestinal epithelial cells. The current studies used rats sensitized to horseradish peroxidase (HRP) to define the essential components of this antigen transport system. Sensitization of rats to HRP stimulated increased HRP uptake into enterocytes (significantly larger area of HRP-containing endosomes) and more rapid transcellular transport compared with rats sensitized to an irrelevant protein or naive control rats. Whole serum but not IgE-depleted serum from sensitized rats was able to transfer the enhanced antigen transport phenomenon. Immunohistochemistry demonstrated that sensitization induced expression of CD23, the low-affinity IgE receptor (FcepsilonRII), on epithelial cells. The number of immunogold-labeled CD23 receptors on the enterocyte microvillous membrane was significantly increased in sensitized rats and was subsequently reduced after antigen challenge when CD23 and HRP were localized within the same endosomes. Finally, pretreatment of tissues with luminally added anti-CD23 antibody significantly inhibited both antigen transport and the hypersensitivity reaction. Our results provide evidence that IgE antibodies bound to low-affinity receptors on epithelial cells are responsible for the specific and rapid nature of this novel antigen transport system.
Impaired TrkB Receptor Signaling Underlies Corticostriatal Dysfunction in Huntington’s Disease
Authors: Joshua L. Plotkin, Michelle Day, Jayms D. Peterson, Zhong Xie, Geraldine J. Kress, Igor Rafalovich, Jyothisri Kondapalli, Tracy S. Gertler, Marc Flajolet, Paul Greengard, Mihaela Stavarache, Michael G. Kaplitt, Jim Rosinski, C. Savio Chan, D. James Surmeier
Journal: Neuron (2014)

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The debilitating choreic movements that plague HD patients have been attributed to striatal degeneration induced by the loss of cortically supplied brain-derived neurotrophic factor (BDNF). Here, we show that in mouse models of early symptomatic HD, BDNF delivery to the striatum and its activation of tyrosine-related kinase B (TrkB) receptors were normal. However, in striatal neurons responsible for movement suppression, TrkB receptors failed to properly engage postsynaptic signaling mechanisms controlling the induction of potentiation at corticostriatal synapses. Plasticity was rescued by inhibiting p75 neurotrophin receptor (p75NTR) signaling or its downstream target phosphatase-and-tensin-homolog-deleted-on-chromosome-10 (PTEN). Thus, corticostriatal synaptic dysfunction early in HD is attributable to a correctable defect in the response to BDNF, not its delivery.
Rehabilitation After Cardiac Surgery
Authors: Solomon Fisch
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The enlightening article by Rimm et al (236:361, 1976) evokes other thoughts. I wonder if they have been considered by evaluators of coronary bypass efficacy in angina pectoris. To the well-known placebo responses to medicinal and surgical therapies of angina, which can be as high as 60%, one must now consider the contribution made by the postoperative occupational changes described by these authors. Calculations from their data showed that about 27% of those less than and 46% of those more than 55 years of age either retired or changed to a lesser occupational demand. This change per se can be a factor in diminishing the daily anginal attack rate. The authors' bar graph would seem to indicate that this may be even more significant, because those engaged in the heavier types of work constituted the bulk of those switching to lighter physical demands. Those in the sedentary
NEURASTHENIA CURED BY EXERCISE AND FORCED FEEDING.REPORT OF TWO CASES.
Authors: EDWARD LIVINGSTON HUNT
Journal: JAMA (1905)

In the two cases of neurasthenia reported in this article, one patient was treated in a hotel, the other in his own home in, New York. They were both treated by the simple method of exercise and forced feeding. These methods were employed at a time when rest-cures, with restricted diet and isolation and sanitaria, were universally employed. In the first case, all hope of recovery had been abandoned, and in the second, the court had signed the commitment papers. Both patients completely recovered. <h3>Case 1.</h3> A. B., aged 45, married, father of two healthy children, engaged in business. <h3>History.</h3> As a child he was well, except for the ordinary diseases of infancy; as a boy and youth he was strong, healthy, and in every respect normal. There was no history or indication of any serious or prolonged illness. His father was living and his heredity
Skin prick test reactions to brewer's yeast (<i>Saccharomyces cerevisiae</i>) in adult atopic dermatitis patients
Authors: O. Kortekangas‐Savolainen, K. Lammintausta, K. Kalimo
Journal: Allergy (1993)

The sensitizing capacity of brewer's yeast ( Saccharomyces cerevisiae ) was studied with the skin prick test method in 449 subjects, including 226 atopic dermatitis (AD) patients, 50 patients with allergic rhinitis (AR) and/or asthma (A), and 173 nonatopic controls. A positive SPT reaction (≥++) was seen in 94% of patients with severe AD, in 76% with moderate AD, and in 25% with mild AD or no history of AD. Patients with AR and/or A and nonatopic controls displayed a positive reaction in only 8 and 2% of cases, respectively. There was also a parallel skin prick test reactivity with other yeasts including Pityrosporum ovale and Candida albicans , suggesting cross‐reactivity. Parallel skin reactivity was observed also with molds and animal dander but not with pollen or house‐dust mite. A significant correlation was also found between total serum IgE level and skin prick test (SPT) results with S. cerevisiae .