tbuckley/cabot-search huggingface dataset:
Liverpool care pathway: doctors have always aimed to ease distress in dying
Authors: B. Murray
Journal: BMJ (2012)

Some years ago I was working as a junior doctor in a busy teaching hospital in northwest England. I was part of a team in a regional renal unit. We had many patients with end stage renal failure. On regular dialysis many had no hope of recovery; some had unsuccessful renal transplants, and many were too unwell to be considered for a transplant.

After years of itching, twitching, failed fistulas, infections, nausea, oedema, and breathlessness, some patients would reach the inevitable end stage. The senior registrar with whom I worked was a former army officer. We worked in a rigid regime of discipline and protocol, and I remember wondering aloud to the consultant if I had joined the armed forces. This approach to the management of the patients, however, was effective and efficient. Nothing was missed, and all data were recorded in rigid fashion. I was taught a discipline to carry with me throughout my working life.

You might think that this obsessive approach would leave little room for compassion. Quite the opposite. Once all criteria pointed to the end of life, as all options had failed, a further set of rules applied. The family was summoned, nurses were called in, and this commanding officer would become …
Inducible mutant huntingtin expression in HN10 cells reproduces Huntington's disease-like neuronal dysfunction
Authors: Andreas Weiss, Ana Roscic, Paolo Paganetti
Journal: Molecular Neurodegeneration (2009)

Expansion of a polyglutamine repeat at the amino-terminus of huntingtin is the probable cause for Huntington's disease, a lethal progressive autosomal-dominant neurodegenerative disorders characterized by impaired motor performance and severe brain atrophy. The expanded polyglutamine repeat changes the conformation of huntingtin and initiates a range of pathogenic mechanisms in neurons including intracellular huntingtin aggregates, transcriptional dysregulation, energy metabolism deficits, synaptic dystrophy and ultimately neurodegeneration. It is unclear how these events relate to each other or if they can be reversed by pharmacological intervention. Here, we describe neuronal cell lines expressing inducible fragments of normal and mutant huntingtin.In HN10 cells, the expression of wild type and mutant huntingtin fragments was dependent on the induction time as well as on the concentration of the RheoSwitch(R) inducing ligand. In order to analyze the effect of mutant huntingtin expression on cellular functions we concentrated on the 72Q exon1 huntingtin expressing cell line and found that upon induction, it was possible to carefully dissect mutant huntingtin-induced phenotypes as they developed over time. Dysregulation of transcription as a result of mutant huntingtin expression showed a transcription signature replicating that reported in animal models and Huntington's disease patients. Crucially, triggering of neuronal differentiation in mutant huntingtin expressing cell resulted in the appearance of additional pathological hallmarks of Huntington's disease including cell death.We developed neuronal cell lines with inducible expression of wild type and mutant huntingtin. These new cell lines represent a reliable in vitro system for modeling Huntington's disease and should find wide use for high-throughput screening application and for investigating the biology of mutant huntingtin.
Offending in psychiatric patients after discharge from medium secure units: Conviction rate may be misleading
Authors: Steffan Davies, Martin Clarke, Conor Duggan
Journal: BMJ (2004)

EDITOR—Offending by psychiatric patients is of great public concern, and offending by former patients in medium secure units who are, or should be, receiving psychiatric supervision in the community is particularly interesting. The paper by Maden et al, although a welcome addition to the literature, obscures important aspects of the issue …
Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma
Authors: Makoto Chuma, Michiie Sakamoto, Jun Yasuda, Gen Fujii, Kazuaki Nakanishi, Akira Tsuchiya, Tsutomu Ohta, Masahiro Asaka, Setsuo Hirohashi
Journal: Journal of Hepatology (2004)
Skeletal muscle expression and abnormal function of beta-myosin in hypertrophic cardiomyopathy.
Authors: G Cuda, L Fananapazir, W S Zhu, J R Sellers, N D Epstein
Journal: Journal of Clinical Investigation (1993)

Hypertrophic cardiomyopathy is an important inherited disease. The phenotype has been linked, in some kindreds, to the beta-myosin heavy chain (beta-MHC) gene. Missense and silent mutations in the beta-MHC gene were used as markers to demonstrate the expression of mutant and normal cardiac beta-MHC gene message in skeletal muscle of hypertrophic cardiomyopathy patients. Mutant beta-myosin, also shown to be present in skeletal muscle by Western blot analysis, translocated actin filaments slower than normal controls in an in vitro motility assay. Thus, single amino acid changes in beta-myosin result in abnormal actomyosin interactions, confirming the primary role of missense mutations in beta-MHC gene in the etiology of hypertrophic cardiomyopathy.
Peripheral blood remission of hairy cell leukemia after transfusion hepatitis
Authors: Michael J. Keefer, Maril J. Weber, Sylvia S. Bottomley, Dilip L. Solanki, Thomas A. Hosty
Journal: American Journal of Hematology (1987)

Abstract Hairy cell leukemia is a chronic lymphoproliferative disorder characterized clinically by splenomegaly and cytopenias. Spontaneous remissions are rare and splenectomy is often performed when the blood counts worsen and cause symptoms. Three of our patients with hairy cell leukemia developed recurrent pancytopenia and transfusiondependent anemia after splenectomy. Each subsequently acquired transfusion hepatitis and in two patients marked hematologic improvement was noted within 2 months. Complete peripheral blood remission occurred within 17 months in all patients although bone marrow infiltration with hairy cells persisted. One patient remains in remission for 12 years; the other two succumbed to infectious illnesses but with normal blood counts. The mechanism by which hepatitis virus induces hematologic recovery in patients with hairy cell leukemia is unknown but may involve augmentation of the interferon system.
Drugs, Like Cigarette Smoking, Can Be Dangerous
Authors: Hugh H. Hussey
Journal: JAMA (1976)

"Warning: The Surgeon General Has Determined That Cigarette Smoking Is Dangerous to Your Health." These words, printed on every package of cigarettes sold in the United States for a decade or so, were the outcome of a decision based on a study by an advisory committee on "Smoking and Health." The warning, of course, resulted from promulgation of a federal regulation. Since then, nothing has been revealed that would undermine the wisdom of the committee's report or the surgeon general's decision. Indeed, supportive evidence has mounted. The two federal agencies that have much to do with issuing regulations on matters of health and medical practice are the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC). Recently, the FTC has decided that, for the good of the public health, physicians must advertise. Whatever that means, physicians generally have resented what they deem an intrusion. Also recently, the FDA
Sister chromatid exchanges in lymphocytes of psoriatics after treatment with 8-methoxypsoralen and long wave ultraviolet radiation
Authors: D. MOURELATOS, M.J.W. FAED, P.W. GOULD, B. E.JOHNSON, W. FRAIN-BELL
Journal: British Journal of Dermatology (1977)

Sister chromatid exchange rates in cultured cells from the blood of patients receiving photochemotherapy have been examined as an indicator of possible genetic hazards of the treatment to patients with psoriasis. Lymphocytes of untreated patients with psoriasis appear to have sister chromatid exchange rates after 72 h of culture indistinguishable from normal subjects and there is no evidence from these studies that sister chromatid exchanges are significantly increased in the lymphocytes of patients receiving photochemotherapy. Cells from blood taken from patients who had been given 8-methoxypsoralen orally 2 h before and then irradiated with UV-A in vitro were found to have an increased exchange rate which could be related to the presence of the drug in the peripheral circulation.
Physiological Effects of High Pressures of Nitrogen and Oxygen
Authors: WALLACE O. FENN
Journal: Circulation (1962)

A brief survey is given of the effects of different pressures on living organisms. High-oxygen partial pressures inhibit oxidative metabolism and, according to Gerschman, have effects which summate at some point with the effects of radiation. In a study of the mechanism of the narcotic effect of inert gases, it was found that high pressures of nitrogen and argon, but not helium, act like other anestheties in favoring water-in-oil rather than oil-in-water emulsion of dilute NaOH solutions and olive oil. The effect is small but appears to be real. This suggests that inert gases may make the lipoidal surface layer of cells relatively more continuous and therefore less permeable.
Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action.
Authors: B M Hall, N W Pearce, K E Gurley, S E Dorsch
Journal: The Journal of Experimental Medicine (1990)

The cellular basis of the specific unresponsiveness that develops in DA rats treated with cyclosporine (CSA) for 10 d after grafting a PVG heart was examined using an adoptive transfer assay. CD4+ cells from rats with long survival grafts specifically lack the capacity to restore PVG heart graft rejection, and can also inhibit the capacity of naive T cells to restore rejection, while in the first few weeks post-transplant, both CD4+ and CD8+ T cells from CSA-treated hosts have the capacity to effect PVG graft rejection. In this study, we demonstrated the CD4+ suppressor cells also had the capacity to inhibit restoration of rejection by CD4+ cells from CSA-treated DA rats recently transplanted with PVG hearts, and from rats sensitized to third party, but not from those specifically sensitized to PVG. They also inhibited the capacity of both naive CD8+ and sensitized CD8+ cells to effect rejection. These results showed that the CD4+ suppressor cell was capable of overriding the capacity to effect rejection of the CD4+ cell and activated CD8+ cells that were present in the CSA-treated host shortly after transplantation. The failure of naive CD8+ cells to augment suppression and the capacity of CD4+ suppressor cells to transfer unresponsiveness to irradiated hosts in which regeneration of CD8+ cells was abolished by thymectomy suggested that it was the CD4+ cell alone that mediated suppression. However, the failure of CD4+ suppressor cells to reinduce unresponsiveness in irradiated hosts whose CD8+ cells had been depleted by therapy with the mAb MRC Ox8 showed that a radioresistant CD8+ cell was required to reestablish the state of specific unresponsiveness. The induction of CD4+ suppressor cells in thymectomized hosts suggested that these cells were derived from long-lived CD4+ lymphocytes. However, their sensitivity to cyclophosphamide and their loss of suppressor function both after removal of the graft and after 3 d in culture demonstrated that the suppressor cell itself had a short lifespan. The CD4+ suppressor was shown to be MRC Ox22+ (CD45R+), MRC Ox17+ (MHC class II), and MRC Ox39+ (CD25, IL-2-R). These studies demonstrated the CD4+ suppressive cell identified in rats with specific unresponsiveness induced by CSA therapy had many features of the suppressor inducer cell identified in in vitro studies of the alloimmune response.(ABSTRACT TRUNCATED AT 400 WORDS)
Selective depletion of alloreactive T cells by targeted therapy of heat shock protein 90: a novel strategy for control of graft-versus-host disease
Authors: Claudia Stuehler, Stephan Mielke, Manik Chatterjee, Johannes Duell, Sarah Lurati, Florian Rueckert, Hermann Einsele, Ralf C. Bargou, Max S. Topp
Journal: Blood (2009)
The fibromatoses: a clinicopathological concept.
Authors: D H Mackenzie
Journal: BMJ (1972)

Adequate treatment of a disease process involves an under- standing of the natural history of the disease.It is, of course, highly desirable that the aetiology should also be known and it is useful if terminology is sensible and universally accepted.Ignorance of aetiology and variability of nomenclature, however, are not bars to successful treatment provided that in any given instance the evolution of a disease is fully understood.This lecture is concerned with a group of conditions of fibroblastic origin which are known collectively as the fibromatoses.Their aetiology is unknown, but their great importance lies, firstly, in the fact that they are often misdiagnosed as true malignant neoplasms and, secondly, in the sad truth that all too frequently they are very badly treated.Firstly, then, I shall try to define what I mean by a fibro- matosis.Secondly, I shall list those conditions which seem to me to justify the label, and, thirdly, I shall deal briefly with selected examples.Anyone interested in tumours and tumourous conditions of soft tissues knows all too well the vagaries of mesenchymal be- haviour, and it is the fibroblastic line of differentiation that I am concerned with here.Terms such as inflammatory, reactive, or neoplastic while appropriate and accurate in many instances are inadequate to define the behaviour patterns of all fibroblastic proliferations.At least one more category is essential, hence the fibromatoses.This concept has been developed largely since the second world war, and most of the main papers have been in the American literature.Nevertheless, the existence of this strange group of fibroblastic disorders has been known for many years, and Janssen (quoted by Touraine and Ruell) wrote of the "diathese fibroblastique" as long ago as 1902.
Role of endotoxin-responsive macrophages in hepatic injury
Authors: Yasushi Shiratori, Mitsugu Tanaka, Kenji Hai1, Tateo Kawase, Shuichiro Shiina, Tsuneaki Sugimoto
Journal: Hepatology (1990)

Although administration of 100 mg galactosamine caused severe hepatic injury in C3H/HeN mice, splenectomy reduced the grade of this hepatotoxicity. However, this hepatic injury was scarcely detected in the endotoxin-resistant C3H/HeJ mice. In addition, in contrast to high lethality in C3H/HeN mice with a combined administration of galactosamine and endotoxin, splenectomy rendered C3H/HeN mice slightly resistant to this treatment. Further resistance was demonstrated in C3H/HeJ mice. In an attempt to clarify the role of endotoxin-responsive spleen cells in the pathogenesis of hepatic injury, we investigated glactosamine-induced hepatic injury by transfer of lipopolysaccharide-treated C3H/HeN or C3H/HeJ spleen cells. Both oxygen-derived free radical production and the proportion of macrophages in spleen cells were markedly enhanced in C3H/HeN mice after an intraperitoneal injection of lipopolysaccharide. Further increase in oxidative free radical production was found in the dish-adherent cells (macrophages). These enhancements were not demonstrated in lipopolysaccharide-treated C3H/HeJ spleen cells. Athough hepatic injury was not demonstrated in both C3H/HeN and C3H/HeJ mice treated with 35 mg galactosamine alone, severe hepatotoxicity was found in these galactosamine-treated mice when they received lipopolysaccharide-activated C3H/HeN spleen cells, especially macrophages. Simultaneous administration of superoxide dismutase with the activated spleen cells reduced the grade of hepatic injury. On the other hand, hepatic injury was not demonstrated in the galactosamine-treated C3H/HeN or C3H/HeJ mice when they received lipopolysaccharide-treated C3H/HeJ spleen cells, although 3H-galactosamine incorporation into hepatocytes was nearly identical in both C3H/HeN and C3H/HeJ mice. These results suggest that oxidative free radicals of lipopolysaccharide responsive macrophages could contribute to the pathogenesis of galactosamine-induced hepatic injury.
Needle Sticks in Phlebotomists: Too Much Ado About a Rare Event
Authors: J. E. McGowan, D. H. Vroon, M. Cott
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Dr Pate<sup>1</sup>pointed out that the "continuing debate in regard to the magnitude of risks to health care workers involved in treating patients with acquired immunodeficiency syndrome frequently generates dogmatic opinions unsupported by fact." The same can be said for some human immunnodeficiency virus-releated govenmental regulations that are directed at phlebotomists. The major risk for transmission of blood-borne infections during blooddrawing procedures is due to needle sticks, which glove use cannot prevent.<sup>2,3</sup>Despite this, proposed Occupational Safety and Health Aministration guidelines require gloves for all phlebotomists for all procedures whereexposure to blood is possible.<sup>4</sup>This proposal ignores recommendations from the Centers for Disease Control that skilled phlebotomists be given the choice of whether or not to wear gloves.<sup>5</sup>Phlebotomy rarely involves worker contact with body fluids, except when the employee is inexperienced or has sores or dermatologic conditions of the hands; in
Exposure of the U.S. Population to Bisphenol A and 4- <i>tertiary</i> -Octylphenol: 2003–2004
Authors: Antonia M. Calafat, Xiaoyun Ye, Lee-Yang Wong, John A. Reidy, Larry L. Needham
Journal: Environmental Health Perspectives (2007)

BackgroundBisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States.ObjectivesWe aimed to assess exposure to BPA and tOP in the U.S. general population.MethodsWe measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants ≥ 6 years of age in the 2003–2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry.ResultsBPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p &lt; 0.001), who in turn had higher concentrations than adults (p = 0.003). LSGM concentrations were lowest for participants in the high household income category (&gt; $45,000/year).ConclusionsUrine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.
Familial aggregation of asthma in a South Bavarian population.
Authors: E von Mutius, T Nicolai
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

There is considerable evidence for a significant hereditary component in the pathogenesis of asthma and allergic diseases. The objective of this study was to investigate familial influences unique to the expression of asthma. School children (n = 9,403), 9 to 11 yr of age, were enrolled in a cross-sectional survey in southern Germany. The prevalence of asthma and allergic diseases in parents and children was assessed through parental questionnaires. Atopic sensitization was measured by skin prick tests, and bronchial responsiveness was determined by cold air hyperventilation challenge. The prevalence of asthma alone, i.e., without concomitant hay fever or atopic eczema, increased strongly if nearest of kin suffered from asthma alone (4.7 versus 11.7%, p < 0.0001). A family history of hay fever or atopic dermatitis, excluding asthma, was unrelated to asthma in the offspring (4.7 versus 3.9%). These relations did not change when stratifying for skin prick test reactivity (STR) and bronchial hyperresponsiveness (BHR). STR alone and BHR alone (i.e., without manifestation of disease) were unrelated to a family history of asthma or allergy. The results strongly suggest a separate genetic factor controlling the development of asthma. Skin test positivity and BHR to cold, dry air are unlikely to be the underlying mechanisms through which the inheritance of childhood asthma is transmitted.
Metabolism of diffuse intrinsic brainstem gliomas in children
Authors: Ashok Panigrahy, Marvin D. Nelson, Jonathan L. Finlay, Richard Sposto, Mark D. Krieger, Floyd H. Gilles, Stefan Blüml
Journal: Neuro-Oncology (2007)

Progress in the development of effective therapies for diffuse intrinsic brainstem gliomas (DIBSGs) is compromised by the unavailability of tissue samples and the lack of noninvasive markers that can characterize disease status. The purpose of this study was to compare the metabolic profile of DIBSGs with that of astrocytomas elsewhere in the CNS and to determine whether the measurement of metabolic features can improve the assessment of disease status. Forty in vivo MR spectroscopy (MRS) studies of 16 patients with DIBSG at baseline and after radiation therapy were retrospectively reviewed. Control data for baseline studies of DIBSGs were obtained from 14 untreated regular and anaplastic astrocytomas. All spectra were acquired with single-voxel, short echo-time (35 ms), point-resolved spectroscopy. Absolute metabolite concentrations (mmol/kg) and lipid intensities (arbitrary units) were determined. At baseline, creatine and total choline (tCho) were significantly lower in DIBSGs than in astrocytomas elsewhere in the CNS (4.3 +/- 1.1 vs. 7.5 +/- 1.9 mmol/kg, p < 0.001; 1.9 +/- 0.7 vs. 4.2 +/- 2.6, p < 0.001). Serial MRS in individual subjects revealed increasing levels of tCho (p < 0.05) and lipids (p < 0.05) and reduced ratios of N-acetylaspartate, creatine, and myoinositol relative to tCho (all p < 0.01). Metabolic progression defined by increased tCho concentration in serial MRS preceded clinical deterioration by 2.4 +/- 2.7 months (p < 0.04). Low tCho of DIBSG at baseline is consistent with low proliferative tumors. Subsequent metabolic changes that have been associated with malignant degeneration preceded clinical deterioration. MRS provides early surrogate markers for disease progression.
Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients
Authors: Jason L. Gaglia, Alexander R. Guimaraes, Mukesh Harisinghani, Stuart E. Turvey, Richard Jackson, Christophe Benoist, Diane Mathis, Ralph Weissleder
Journal: Journal of Clinical Investigation (2010)

Type 1A diabetes (T1D) is an autoimmune disease characterized by leukocyte infiltration of the pancreatic islets of Langerhans. A major impediment to advances in understanding, preventing, and curing T1D has been the inability to “see” the disease initiate, progress, or regress, especially during the occult phase. Here, we report the development of a noninvasive method to visualize T1D at the target organ level in patients with active insulitis. Specifically, we visualized islet inflammation, manifest by microvascular changes and monocyte/macrophage recruitment and activation, using magnetic resonance imaging of magnetic nanoparticles (MNPs). As a proof of principle for this approach, imaging of infused ferumoxtran-10 nanoparticles permitted effective visualization of the pancreas and distinction of recent-onset diabetes patients from nondiabetic controls. The observation that MNPs accumulate in the pancreas of T1D patients opens the door to exploiting this noninvasive imaging method to follow T1D progression and monitoring the ability of immunomodulatory agents to clear insulitis.