tbuckley/cabot-search huggingface dataset:
Functional Imaging in Extrapulmonary Sarcoidosis
Authors: Michael Soussan, Alexandre Augier, Pierre-Yves Brillet, Pierre Weinmann, Dominique Valeyre
Journal: Clinical Nuclear Medicine (2013)

Sarcoidosis is a multiorgan granulomatous disease of unknown etiology that primarily involves the lungs and the lymphatic system. Extrapulmonary sarcoidosis is common, occurring in 30 to 50% of patients. In this review, we describe and illustrate the role of F-FDG PET/CT and MR imaging in patients with extrapulmonary sarcoidosis. FDG-PET/CT and MR can improve the accuracy of the diagnosis of extrapulmonary involvement, specify the respective contributions of active and fibrotic components of lesions, guide the selection of the biopsy site, provide prognostic information, and guide therapeutic management. We focus on suggestive patterns that help to improve lesion characterization, especially when these lesions are clinically occult. In cardiac sarcoidosis, the combined use of FDG-PET/CT and cardiac MR may provide optimal detection of the disease by enabling the differentiation between patients with active granulomatous inflammation and those with fibrous lesions. In cases with central nervous system involvement, the T2 hypointensity of the dural and parenchymal lesions is helpful for identifying sarcoidosis. Granulomatous bone marrow infiltration in the axial skeleton can be sensitively detected by both FDG-PET/CT and MR. Muscular sarcoidosis can have a characteristic appearance with the "dark star" sign on MR and a thick linear FDG uptake that predominantly involves the lower legs, designated as the "tiger man" sign. Extrathoracic lymphadenopathy is commonly observed on FDG-PET/CT imaging; however, its features are not specific, and the differentiation of extrathoracic lymphadenopathy from metastatic disease, tuberculosis, or lymphoma may be difficult. Familiarity with the functional imaging features in extrapulmonary sarcoidosis in various anatomical locations plays a crucial role in the diagnosis and management of patients.
The Diverse Effects of Iodide on Thyroid Function
Authors: Robert D. Utiger
Journal: New England Journal of Medicine (1972)

The extraordinarily diverse effects of iodide on thyroid hormone formation and secretion have interested and puzzled both clinicians and basic scientists for years, Iodide is an unusual substance in that its intake, in quantities in the order of 50 to 500 μg daily, is clearly essential for normal thyroid hormone formation and secretion. On the other hand, iodide has been shown to have multiple antithyroid actions. The anti-thyroid actions of iodide include inhibition of iodide organification, thus reducing thyroid hormone synthesis, and inhibition of release of stored thyroid hormone, which results in diminished thyroid hormone secretion and reduced plasma thyroid . . .
Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice
Authors: Guanhua Xie, Gamze Karaca, Marzena Swiderska-Syn, Gregory A. Michelotti, Leandi Krüger, Yuping Chen, Richard T. Premont, Steve S. Choi, Anna Mae Diehl
Journal: Hepatology (2013)

Liver repair involves phenotypic changes in hepatic stellate cells (HSCs) and reactivation of morphogenic signaling pathways that modulate epithelial-to-mesenchymal/mesenchymal-to-epithelial transitions, such as Notch and Hedgehog (Hh). Hh stimulates HSCs to become myofibroblasts (MFs). Recent lineage tracing studies in adult mice with injured livers showed that some MFs became multipotent progenitors to regenerate hepatocytes, cholangiocytes, and HSCs. We studied primary HSC cultures and two different animal models of fibrosis to evaluate the hypothesis that activating the Notch pathway in HSCs stimulates them to become (and remain) MFs through a mechanism that involves an epithelial-to-mesenchymal–like transition and requires cross-talk with the canonical Hh pathway. We found that when cultured HSCs transitioned into MFs, they activated Hh signaling, underwent an epithelial-to-mesenchymal–like transition, and increased Notch signaling. Blocking Notch signaling in MFs/HSCs suppressed Hh activity and caused a mesenchymal-to-epithelial–like transition. Inhibiting the Hh pathway suppressed Notch signaling and also induced a mesenchymal-to-epithelial–like transition. Manipulating Hh and Notch signaling in a mouse multipotent progenitor cell line evoked similar responses. In mice, liver injury increased Notch activity in MFs and Hh-responsive MF progeny (i.e., HSCs and ductular cells). Conditionally disrupting Hh signaling in MFs of bile-duct–ligated mice inhibited Notch signaling and blocked accumulation of both MF and ductular cells. Conclusions: The Notch and Hedgehog pathways interact to control the fate of key cell types involved in adult liver repair by modulating epithelial-to-mesenchymal–like/mesenchymal-to-epithelial–like transitions. (Hepatology 2013;58:1801–1813)
Increased oxygen cost of contractility in stunned myocardium of dog.
Authors: Y Ohgoshi, Y Goto, S Futaki, H Taku, O Kawaguchi, H Suga
Journal: Circulation Research (1991)

Recent studies have shown that myocardial oxygen consumption does not proportionally decrease with the deterioration of contractile function in stunned myocardium. To investigate this disproportion, we studied the end-systolic pressure-volume relation and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) in stunned hearts. In the VO2-PVA relation, VO2 can be divided into PVA-dependent and PVA-independent fractions. In excised cross-circulated dog left ventricles, a 15-minute normothermic global ischemia followed by 60-120 minutes of reperfusion significantly decreased the ventricular contractility index (Emax) by approximately 40%, but the PVA-independent VO2 did not significantly decrease. Oxygen cost of PVA, defined as the slope of the VO2-PVA relation, was slightly decreased in stunned hearts. Restoration of the depressed Emax to the preischemic control level by calcium infusion increased the PVA-independent VO2 to 137 +/- 27% of control level (p less than 0.01). Oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased from 0.0011 +/- 0.0003 to 0.0023 +/- 0.0005 ml O2.ml.mm Hg-1.beat-1 per 100 g myocardium in control and stunned hearts, respectively (p less than 0.01). From these new finding, we conclude that the unchanged VO2, despite the depressed contractility in stunned myocardium, is mainly due to the increased oxygen cost of contractility.
Induction of c-ets and c-fos gene expression upon antigenic stimulation of a T cell hybridoma with inducible cytolytic capacity.
Authors: Y Kaufmann, T Silverman, B Z Levi, K Ozato
Journal: The Journal of Experimental Medicine (1987)

Expression of cellular oncogenes was studied in a T cell hybridoma that undergoes cytolytic activation when stimulated by specific antigen or by anti-Thy-1 antibody. The activation occurs without induction of hybridoma proliferation, providing a model to examine oncogene expression during functional differentiation of lymphocytes. We found that c-fos and c-ets-1 mRNAs were transiently induced at high levels in the hybridoma 30 min and 4 h after stimulation, respectively. c-myc and c-ets-2 oncogenes were constitutively expressed in the hybridoma and their mRNA levels were unaffected during 4 h of stimulation, although c-myc expression was reduced in the later stage of stimulation. Inhibitors of T cell activation, cyclosporin A and anti-LFA-1 antibody, blocked the induction of c-fos and c-ets-1 mRNAs without reducing the levels of c-myc and c-ets-2. The results indicate that the functional activation of the CTL hybridoma is associated with induction of c-fos and c-ets-1 genes.
Determinants of Chronic Carbon Dioxide Retention and Its Correction in Humans
Authors: James B. Skatrud, Jerome A. Dempsey, Praful Bhansali, Charles Irvin
Journal: Journal of Clinical Investigation (1980)

17 patients with chronic ventilatory failure (including 14 with chronic obstructive pulmonary disease) were studied to determine the causes of carbon dioxide retention and the chronic effect of medroxyprogesterone acetate on ventilatory drive and acid-base status. Carbon dioxide retention in patients with high mechanical loads occurred concomitantly with a higher than normal inspiratory effort (mouth occlusion pressure) and normal minute ventilation to carbon dioxide production ratio (V̇e/V̇co2); but with shortened inspiratory time (1.3±0.1 vs. 1.8±3 s), increased breathing frequency (17±1 vs. 14±1 breaths/min), low tidal volume (0.57±0.03 vs. 0.88±0.04 L), and high dead space to tidal volume ratio (0.63±0.02 vs. 0.39±0.07). Using a randomized application of treatment and placebo conditions, it was shown that 4 wk of medroxyprogesterone acetate caused significant reductions in Paco2 (from 51±1 to 42±1 mm Hg) in 10 of 17 patients. This “correction” of Paco2 in these patients was associated with increases in mouth occlusion pressure (14%), tidal volume (11%), and alveolar ventilation (15%) compared to placebo, although inspiratory time remained shortened. Arterial and lumbar cerebrospinal fluid pH was alkaline compared to placebo in patients who “corrected” Paco2. No change was noted in lung mechanics or core temperature. Common prerequisites for correction of Paco2 with medroxyprogesterone acetate treatment were the ability to significantly lower Paco2 upon acute voluntary hyperventilation and to increase tidal volume rather than breathing frequency in response to the drug. We attribute chronic CO2 retention in these patients to alterations in respiratory cycle timing and to a neuromuscular inspiratory effort which is adequate for the level of tissue CO2 production, but inadequate in the presence of mechanical and ventilation-perfusion abnormalities to normalize arterial blood gases.
Left ventricular remodeling is the most common cause of systolic dysfunction after acute myocardial infarction: Findings from the stent-PAMI study
Authors: Kishore J. Harjai, Cindy L. Grines, Steve Mattichak, Judith A. Boura, Gregg W. Stone, David Cox, Bruce R. Brodie, William O'Neill
Journal: Journal of the American College of Cardiology (2003)
Predictors of severe H1N1 infection in children presenting within Pediatric Emergency Research Networks (PERN): retrospective case-control study
Authors: S. R. Dalziel, J. M. Thompson, C. G. Macias, R. M. Fernandes, D. W. Johnson, Y. Waisman, N. Cheng, J. Acworth, J. M. Chamberlain, M. H. Osmond, A. Plint, P. Valerio, K. J. Black, E. Fitzpatrick, A. S. Newton, N. Kuppermann, T. P. Klassen
Journal: BMJ (2013)

<b>Objective</b> To identify historical and clinical findings at emergency department presentation associated with severe H1N1 outcome in children presenting with influenza-like illness. <b>Design</b> Multicentre retrospective case-control study. <b>Setting</b> 79 emergency departments of hospitals associated with the Pediatric Emergency Research Networks in 12 countries. <b>Participants</b> 265 children (&lt;16 years), presenting between 16 April and 31 December 2009, who fulfilled Centers for Disease Control and Prevention criteria for influenza-like illness and developed severe outcomes from laboratory confirmed H1N1 infection. For each case, two controls presenting with influenza-like illness but without severe outcomes were included: one random control and one age matched control. <b>Main outcome measures</b> Severe outcomes included death or admission to intensive care for assisted ventilation, inotropic support, or both. Multivariable conditional logistic regression was used to compare cases and controls, with effect sizes measured as adjusted odds ratios. <b>Results</b> 151 (57%) of the 265 cases were male, the median age was 6 (interquartile range 2.3-10.0) years, and 27 (10%) died. Six factors were associated with severe outcomes in children presenting with influenza-like illness: history of chronic lung disease (odds ratio 10.3, 95% confidence interval 1.5 to 69.8), history of cerebral palsy/developmental delay (10.2, 2.0 to 51.4), signs of chest retractions (9.6, 3.2 to 29.0), signs of dehydration (8.8, 1.6 to 49.3), requirement for oxygen (5.8, 2.0 to 16.2), and tachycardia relative to age). <b>Conclusion</b> These independent risk factors may alert clinicians to children at risk of severe outcomes when presenting with influenza-like illness during future pandemics.
Photodepletion differentially affects CD4+ Tregs versus CD4+ effector T cells from patients with chronic graft-versus-host disease
Authors: Jean-Philippe Bastien, Gorazd Krosl, Cynthia Therien, Marissa Rashkovan, Christian Scotto, Sandra Cohen, David S. Allan, Donna Hogge, R. Maarten Egeler, Claude Perreault, Denis Claude Roy
Journal: Blood (2010)
A high incidence of Staphylococcus aureus colonization in the external eyes of patients with atopic dermatitis
Authors: Kou Nakata, Yoshitsugu Inoue, Jun Harada, Naoyuki Maeda, Hitoshi Watanabe, Yasuo Tano, Yoshikazu Shimomura, Seiyo Harino, Miki Sawa
Journal: Ophthalmology (2000)
Cancer care commissioning is in chaos since NHS reorganisation, says leading charity
Authors: M. Limb
Journal: BMJ (2014)

The government’s reorganisation of the NHS in England has caused chaos in the commissioning of cancer care services, which now needs radical change to be made fit for purpose, says a report from Cancer Research UK.

The charity said that confused structures, unclear accountability, and loss of national oversight, combined with insufficient funding, threatened to reverse hard won gains in survival rates among people with cancer.

Harpal Kumar, the charity’s chief executive, said that cancer services were now at a “tipping point,” with staff fighting to keep them viable in a context of flatlined budgets and rising demand from patients. “They can’t go on like this with no help or support coming over the horizon,” he said. “And they certainly can’t improve services so that our cancer outcomes are up there with the best in the world.”

The report, published on 8 September, looked at the current state of cancer services, 18 months since NHS reorganisation came into force under the Health and Social Care Act.1 The charity commissioned Birmingham University’s Health Services Management Centre to conduct interviews and surveys among clinicians, commissioners, GPs, experts in public health, and patients.

The …
Leukotrienes as mediators in frog virus 3-induced hepatitis in rats
Authors: Wolfgang Hagmann, Anne-Marie Steffan, André Kirn, Dietrich Keppler
Journal: Hepatology (1987)

The role of leukotrienes was investigated in frog virus 3-induced hepatitis in rats. Frog virus 3 elicited an enhanced generation of cysteinyl leukotrienes in vivo as monitored by measurement of N -acetyl-leukotriene E 4 as the major endogenous metabolite of cysteinyl leukotrienes secreted into rat bile. N -Acetyl-leukotriene E 4 concentrations were elevated for more than 4 hr after frog virus 3 injection. In vitro experiments using cultured rat liver Kupffer cells of high purity indicated that these cells can produce and metabolize leukotrienes and are thus a possible source of leukotrienes elicited in vivo by frog virus 3. The selective 5-lipoxygenase inhibitor AA 861 and the dual inhibitor of arachidonate lipoxygenase and cyclooxygenase, BW 755C, reduced the hepatocellular injury after a high dose of frog virus 3 by about 50 and 80%, respectively, as judged from plasma activities of ALT and sorbitol dehydrogenase at 24 hr after frog virus 3 administration. Our in vivo and in vitro studies argue in favor of an important role of leukotrienes as mediators in frog virus 3 hepatitis in rats.
If Almost Nothing Goes Wrong, Is Almost Everything All Right? Interpreting Small Numerators
Authors: Thomas B. Newman
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Twelve years ago in an article entitled "IfNothing Goes Wrong, Is Everything All Right?" Drs Hanley and Lippman-Hand<sup>1</sup>provided a helpful rule of thumb for interpreting numerators of 0. They showed that if 0 events are observed in N trials, the upper limit of the 95% confidence interval (CI) for the frequency of events is approximately 3/N. Thus, if there are no deaths among 50 patients treated with a new medication, the upper limit of the 95% CI for the risk of death is about 3/50, or 6%. On the other hand, if no deaths occur in a study of 1000 patients, the upper limit of the 95% CI for the mortality rate is 3/1000, or 0.3%. I have found that similar approximations work for other small numerators and that they can be a helpful shortcut when scanning journal articles. In each case, as the denominator
Papillomavirus E2 Protein Induces Expression of the Matrix Metalloproteinase-9 via the Extracellular Signal-Regulated Kinase/Activator Protein-1 Signaling Pathway
Authors: Andreas Behren, Christian Simon, Roxana Michaela Schwab, Ekaterina Loetzsch, Stephan Brodbeck, Evamaria Huber, Frank Stubenrauch, Hans Peter Zenner, Thomas Iftner
Journal: Cancer Research (2005)

Abstract Papillomaviruses are involved in the development of cancers of the female cervix, head and neck, and skin. An excellent model to study papillomavirus-induced tumor induction and progression is the New Zealand White rabbit, where the skin is infected with the cottontail rabbit papillomavirus (CRPV). This leads to the formation of benign tumors that progress into invasive and metastasizing carcinomas without the need for cofactors. We have shown previously that specific mutations in the transactivation domain of the transcription/replication factor E2 cause a dramatic loss in the tumor induction efficiency of the viral genome and a major deficiency in tumor progression as we show now. By comparing wild-type (WT) and mutant E2-induced skin tumors, we found high levels of matrix metalloproteinase-9 (MMP-9) protein and transcripts in WT CRPV-E2–induced tumors in contrast to certain mutant CRPV-E2–induced papillomas and normal uninfected skin. Stable cell lines and reporter assays revealed that E2 from different papillomavirus types is able to transactivate the MMP-9 promoter via the promoter-proximal activator protein-1 (AP-1) site as shown in reporter gene assays with mutant MMP-9 promoter constructs. Furthermore, WT E2 but not mutant E2 strongly transactivated a minimal promoter reporter construct with multiple AP-1 sites. The MMP-9 protein induced in cells expressing E2 degrades collagen matrices as measured in Matrigel-based invasion/mobility assays. E2-induced MMP-9 expression can be blocked by a chemical inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase 1 (PD 098059), suggesting that E2 activates the MAPK/ERK signaling pathway, which is further supported by the induction of ERK1 in CRPV-E2–transfected cells. (Cancer Res 2005; 65(24): 11613-21)
Hugh Sinclair and the study of nutrition
Authors: G. R Wadsworth
Journal: Journal of the Royal Society of Medicine (2002)

In her biography of Hugh Sinclair1, Jeanette Ewin refers to his letter entitled, ‘Deficiency of fatty acids and atherosclerosis, etcetera’ published in The Lancet in 1956. This communication cited evidence that, in rats, absence of particular chemical constituents of fats from the diet led to accumulation of cholesterol in blood vessels. Though controversial the letter stimulated new interest in possible associations between diet and health; it helped to extend the scope of nutritional studies beyond diseases such as beriberi, scurvy and rickets, associated with a deficient intake of particular vitamins or minerals.

Reviewing Ewin's book, Professor Andre McLean provides information of particular interest about Sinclair as a person (May 2002 JRSM2). Clearly, Sinclair was an eccentric, unable to find a comfortable niche within traditional academic departments; but there was another reason for his difficulties—namely, that the study of nutrition as a discipline then becoming apparent had its own philosophy and scope of inquiries which were not provided for in universities at that time. This was probably the true motivation for Sinclair's sad efforts during most of his academic life to establish an institute of human nutrition.

The science of nutrition must be based on the study of the anatomical, physiological, and pathological characteristics of individuals as these are influenced by the diet. These characteristics are determined not only by the diet but also by genetics, socioeconomic circumstances, exposure to infections and possibly other influences. No disease develops because of a single cause but because of interactions within a web of factors of which the diet may sometimes be one. Separate components of the web are not always present at the same time and one factor may permit or inhibit an effect of another at a future time.

The characteristics of an individual and their modification by diet, exposure to infections, bombardment of tissues by free radicals and other circumstances will influence the natural history of a disease. A clear understanding of this progression will require precise observations of numerous kinds, including frequent measurements of the amounts and kinds of food consumed. An institute of nutrition, as envisaged by Hugh Sinclair, might fulfil these requirements if it was dedicated to the study of cohorts of individuals, ideally from birth until death.
The Economic Costs of Stroke in Massachusetts
Authors: Elizabeth Mills, Mark Thompson
Journal: New England Journal of Medicine (1978)

The morbid and mortal harm of strokes may be reduced by public-health programs addressed to the underlying risk factors — particularly the early diagnosis and control of hypertension — as well as by medical management of the condition. The benefits of such programs are alleviation of both the human and the economic costs of stroke. Although a consideration of both cost categories is critical to effective public-health policy, only the economic consequences can be measured. Of economic costs, the more evident and readily measured are the direct costs: hospital expenses, fees for physician visits, nursing-home charges and the like. Less . . .
DDT and Breast Cancer in Young Women: New Data on the Significance of Age at Exposure
Authors: Barbara A. Cohn, Mary S. Wolff, Piera M. Cirillo, Robert I. Sholtz
Journal: Environmental Health Perspectives (2007)

Previous studies of DDT and breast cancer assessed exposure later in life when the breast may not have been vulnerable, after most DDT had been eliminated, and after DDT had been banned.We investigated whether DDT exposure in young women during the period of peak DDT use predicts breast cancer.We conducted a prospective, nested case-control study with a median time to diagnosis of 17 years using blood samples obtained from young women during 1959-1967. Subjects were members of the Child Health and Development Studies, Oakland, California, who provided blood samples 1-3 days after giving birth (mean age, 26 years). Cases (n = 129) developed breast cancer before the age of 50 years. Controls (n = 129) were matched to cases on birth year. Serum was assayed for p,p'-DDT, the active ingredient of DDT; o,p'-DDT, a low concentration contaminant; and p,p'-DDE, the most abundant p,p'-DDT metabolite.High levels of serum p,p'-DDT predicted a statistically significant 5-fold increased risk of breast cancer among women who were born after 1931. These women were under 14 years of age in 1945, when DDT came into widespread use, and mostly under 20 years as DDT use peaked. Women who were not exposed to p,p'-DDT before 14 years of age showed no association between p,p'-DDT and breast cancer (p = 0.02 for difference by age).Exposure to p,p'-DDT early in life may increase breast cancer risk. Many U.S. women heavily exposed to DDT in childhood have not yet reached 50 years of age. The public health significance of DDT exposure in early life may be large.