tbuckley/cabot-search huggingface dataset:
A lipid to treat non-alcoholic fatty liver disease – The dawn of ‘lipo-rehabilitation’?
Authors: Q.M. Anstee, C.P. Day
Journal: Journal of Hepatology (2011)

Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl sidechains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatictriglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.
Another five year plan for the NHS
Authors: C. Ham
Journal: BMJ (2009)

<h3>Introduction</h3> If immunosuppressant therapy (IST) is withdrawn in patients with autoimmune hepatitis (AIH) when remission is achieved, 50–70% will have a disease relapse within 12 months. Thus, many patients receive long-term maintenance IST. However, IST has potential side effects, including an increased cancer risk. Recent studies suggest a lower AIH relapse rate if IST is withdrawn at a later stage in the disease. Data are lacking in regard to long-term outcome following IST withdrawal. <h3>Methods</h3> Retrospective audit of long-term outcome of AIH following withdrawal of IST. A total of 282 patients with definite or probable AIH by International AIH Group criteria, had presented to our Unit between 1971–2015 and had achieved normalisation of serum ALT within 12 months of starting IST (prednisolone plus azathioprine, or mycophenolate if azathioprine intolerant). From these, we found 25 patients in whom all IST was subsequently discontinued. We assessed outcome in these patients, in comparison to those who continued IST. Follow-up was until last serum ALT for calculating relapse rate and until death or last known to be alive for calculating survival rates. <h3>Results</h3> The 25 patients (21 female, age at diagnosis 50 (8–68) years) had been on IST before withdrawal for 3.9 (0.1–22.4) years. Five had cirrhosis at presentation. All patients had normal serum ALT and globulins at time of withdrawal except one patient with acute pancreatitis. Reasons for IS withdrawal were: cancer (6), infections (3), side effects (4), frailty (6) patient choice (6), doubt about diagnosis (subsequently resolved) (1). Relapses occurred in 7 patients (28%) after 1.6 (0.5–9.6) years. Relapse rates were 15%, 20% and 28% after 2, 5 and 10 years respectively. All patients achieved re-normalisation of serum ALT within 3 months of re-starting therapy (prednisolone 10–40 mg/day) plus (in 5 patients) azathioprine or mycophenolate, subsequently continued as maintenance therapy. Over follow up (from IST withdrawal) of 4.2 (1.2–25.1 years), no patient developed liver decompensation, variceal bleeding or hepatocellular carcinoma. Six patients died after 4 (3.3–15.9) years; none due to liver disease or following AIH relapse. Patients stopping IST (n = 25) had, compared to those who continued IST (n = 257) higher 10- and 20 year survival (99±4% and 79±9% respectively vs 78±3% and 48±4% p = 0.021). <h3>Conclusion</h3> In patients with AIH who achieve remission a trial of withdrawal of IS therapy is associated with (a) a lower disease relapse rate than previously reported, (b) no liver adverse events and (c) no reduction in long-term survival compared with patients who continue on long-term IS therapy. <h3>Disclosure of Interest</h3> None Declared
Human <i>Brat</i> Ortholog <i>TRIM3</i> Is a Tumor Suppressor That Regulates Asymmetric Cell Division in Glioblastoma
Authors: Gang Chen, Jun Kong, Carol Tucker-Burden, Monika Anand, Yuan Rong, Fahmia Rahman, Carlos S. Moreno, Erwin G. Van Meir, Constantinos G. Hadjipanayis, Daniel J. Brat
Journal: Cancer Research (2014)

Cancer stem cells, capable of self-renewal and multipotent differentiation, influence tumor behavior through a complex balance of symmetric and asymmetric cell divisions. Mechanisms regulating the dynamics of stem cells and their progeny in human cancer are poorly understood. In Drosophila, mutation of brain tumor (brat) leads to loss of normal asymmetric cell division by developing neural cells and results in a massively enlarged brain composed of neuroblasts with neoplastic properties. Brat promotes asymmetric cell division and directs neural differentiation at least partially through its suppression on Myc. We identified TRIM3 (11p15.5) as a human ortholog of Drosophila brat and demonstrate its regulation of asymmetric cell division and stem cell properties of glioblastoma (GBM), a highly malignant human brain tumor. TRIM3 gene expression is markedly reduced in human GBM samples, neurosphere cultures, and cell lines and its reconstitution impairs growth properties in vitro and in vivo. TRIM3 expression attenuates stem-like qualities of primary GBM cultures, including neurosphere formation and the expression of stem cell markers CD133, Nestin, and Nanog. In GBM stem cells, TRIM3 expression leads to a greater percentage dividing asymmetrically rather than symmetrically. As with Brat in Drosophila, TRIM3 suppresses c-Myc expression and activity in human glioma cell lines. We also demonstrate a strong regulation of Musashi-Notch signaling by TRIM3 in GBM neurospheres and neural stem cells that may better explain its effect on stem cell dynamics. We conclude that TRIM3 acts as a tumor suppressor in GBM by restoring asymmetric cell division.
IMAGINARY CURES FOR IMAGINARY DISEASES
Authors: C. Mercier
Journal: BMJ (1906)

<h3>Abstract</h3> ANP32 proteins, which act as influenza polymerase co-factors, vary between birds and mammals. The well-known mammalian adaptation, PB2-E627K, enables influenza polymerase to use mammalian ANP32 proteins. However, some mammalian-adapted influenza viruses do not harbour this adaptation. Here, we show that alternative PB2 adaptations, Q591R and D701N also allow influenza polymerase to use mammalian ANP32 proteins. PB2-E627K strongly favours use of mammalian ANP32B proteins, whereas D701N shows no such bias. Accordingly, PB2-E627K adaptation emerges in species with strong pro-viral ANP32B proteins, such as humans and mice, while D701N is more commonly seen in isolates from swine, dogs and horses where ANP32A proteins are more strongly pro-viral. In an experimental evolution approach, passage of avian viruses in human cells drives acquisition of PB2-E627K, but not when ANP32B is ablated. The strong pro-viral support of ANP32B for PB2-E627K maps to the LCAR region of ANP32B.
The Cytokines IL-21 and GM-CSF Have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells
Authors: Chi-Keung Wan, Jangsuk Oh, Peng Li, Erin E. West, Elizabeth A. Wong, Allison B. Andraski, Rosanne Spolski, Zu-Xi Yu, Jianping He, Brian L. Kelsall, Warren J. Leonard
Journal: Immunity (2013)
Sources of lead pollution.
Authors: D Gloag
Journal: BMJ (1981)

Environmental lead concentrations today are grossly increased over the natural levels, even far away from cities. Nevertheless, the results of the EEC survey1 (see box) seem reasonably reassuring so far, even for children specially exposed to lead. But even 2% of children exceeding the limit of 1-69 ptmol/l (35 [xg/100 mg) might be too many?that is, if slightly raised levels can cause subtle neurological impairment (see last article, p 1622). Young children tend to have higher blood lead concentrations, which will not be apparent from blood samples taken when they are older. Some studies carried out near factories producing lead pollution have shown considerably raised blood lead concen? trations in many preschool children, and also mothers.2 In Birmingham, although both the schoolchildren and the younger children surveyed had low mean blood concentrations, a worrying proportion of inner city preschool children had concentrations over 1-69 (jtmol/l.3 4 These were mostly Asians and their sources of lead exposure are being investigated, with a detailed dietary survey to look at both dietary lead content and possible nutritional deficiencies that would make them more susceptible to poor environmental conditions.
Collision sports. Injury and repair.: D Fevre. (Pp 280; pound25.00.) Butterworth Heinemann, 1998. ISBN 0-7506-3142-2. Copies can be ordered from Heinemann Customer Services, Direct Mail Department, PO Box 840, Oxford OX2 8YW. Tel: 01865 314627; Fax: 01865 314091.
Authors: Paul D Jackson
Journal: British Journal of Sports Medicine (2000)

Use of imaging data for predicting clinical outcomeEDITOR,-We would like to air three points that arise from the paper Sonographic incidence of tendon microtears in athletes with chronic Achilles tendinosis. 1 Firstly, unfortunately the word "partial" has been omitted from the conclusion (abstract).The conclusion currently reads "There appears to be an association between microtear formation and Achilles tendon rupture".The distinction needs to be made, as the paper's Take home message concludes with the words "There may be a role for ultrasound in identifying athletes at high risk of tendon rupture", and in this case it appears that the authors mean complete tendon rupture.It is important that this ambiguity is clarified.Secondly, although it is well accepted that in many cases tendinosis precedes "spontaneous" tendon rupture, 2 it does not necessarily follow that sonographic abnormality will lead to (complete) tendon rupture.The tissue based pathologies found by Kannus and Jozsa may be more subtle than can be detected by sonography.We feel that, without longitudinal data in a large cohort with an appropriate control group, Gibbon and colleagues are not in a position to draw a conclusion on sonographic screenings of athletes.Thirdly, given the cross sectional study design, the authors should provide caveats emphasising that their theory of tendon remodelling paralleling that of bone is purely speculative.Cross sectional athlete-control comparisons (such as those provided to sustain the argument on tendon remodelling) do not provide evidence of causality-such diVerences can result merely from selection bias.If athlete-control diVerence were causally related, then one could take up basketball in order to grow tall.We emphasise the need for prospectively collected data to predict future outcome.Researchers and clinicians should desist from speculating as to the longitudinal clinical significance of imaging data collected at one point in time only.To our knowledge, there is only one published prospective ultrasonography and clinical correlation study in the tendon literature at present, 3 and it shows rather poor predictive value of ultrasonography in terms of development of symptoms and clinical findings of patellar tendinopathy in female basketball players.Until researchers and reviewers acknowledge the importance of longitudinally collected data for predicting clinical outcome, our imaging field will continue to be mired in a debate based on speculation rather than science.
Prevalence of HTLV-I-associated T-cell lymphoma
Authors: B.J. Poiesz, L.D. Papsidero, G. Ehrlich, M. Sherman, S. Dube, M. Poiesz, K. Dillon, F.W. Ruscetti, D. Slamon, C. Fang, A. Williams, D. Duggan, J. Glaser, A. Gottlieb, J. Goldberg, L. Ratner, P. Phillips, T. Han, A. Friedman-Kien, F. Siegal, K. Rai, A. Sawitsky, L.W.A. Sheremata, H. Dosik, C. Cunningham, R. Montagna
Journal: American Journal of Hematology (2000)

In order to assess the prevalence rate of HTLV-I-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials. Am. J. Hematol. 66:32–38, 2001. © 2001 Wiley-Liss, Inc.
Major journals should peer review trials at protocol stage
Authors: A. Foss, M. Westcott
Journal: BMJ (1997)

Editor—Increasing concern over the poor quality of medical research, and particularly over the conduct of clinical trials, has been voiced by the editors of the major medical journals. This unease has taken expression in the form of the CONSORT statement,1 2 which states the criteria by which a trial should be judged. Unfortunately, most trials are not vigorously assessed until their results are submitted to a journal for publication–a time when it is too late for any errors in trial design to be remedied. There is also the second major problem of negative …
New endoscopic images of mucosal prolapse syndrome
Authors: C. Chen, H. Isomoto, H. Ishii, T. Hayashi, Y. Mizuta, S. Kohno
Journal: Endoscopy (2009)

A 65-year-old man presented with hematochezia and fecal incontinence. For a long time he had been experiencing severe constipation and had needed to train to evacuate the bowels. Conventional colonoscopy revealed a hyperemic broad-based polypoid lesion with central ulceration in the lower rectum ([Fig. 1]). Magnifying colonoscopy with narrow-band image system (NBI) revealed dilated brownish, oval-to-long pits and widening of the pericryptal space around the polypoid lesion ([Fig. 2]). There was no destruction of or irregularity in the pit pattern and no abnormalities in the microvessels. Autofluorescence imaging (AFI) revealed a magenta-colored elevation surrounding the yellowish-green ulcerated area ([Fig. 3]). Histological examination of biopsy specimens taken from the polypoid lesion revealed elongation and distortion of the crypts and fibromuscular obliteration in the mucosa ([Fig. 4]). On the basis of the clinicopathological features, a diagnosis of mucosal prolapse syndrome was made. The patient was successfully treated with bowel retraining to avoid straining at defecation and dependence on laxatives.
Mechanisms of aluminum-induced microcytosis: Lessons from accidental aluminum intoxication
Authors: Carlos A. Caramelo, Jorge B. Cannata, Miguel R. Rodeles, José Luis Fernández Martín, Juan R. Mosquera, Beatriz Monzú, Julio Outeiriño, Guillermina Blum, Concepción Andrea, Antonio J. Lopez Farré, Gonzalo Acuña, Santos Casado, Luis Hernando
Journal: Kidney International (1995)
LANDRY'S PARALYSIS, WITH REPORT OF FIVE CASES.
Authors: J. N. HALL
Journal: JAMA (1907)

Cases of Landry's paralysis are so unusual and in the past have been so indifferently reported that the recent occurrence of three cases in our practice, of one case kindly reported to us by Dr. H. W. Kirby, Georgetown, Colo., and of a fifth case by Dr. C. F. Wolfer, Louisville, Colo., leads us to report them, with a review of the literature for the past year. There seems to be no general agreement as to just what cases should be included under the term acute ascending paralysis. In the literature we have found a number of cases reported under this head that were obviously myelitis, poliomyelitis, or multiple neuritis. In our report we shall consider as typical only those cases characterized by acute onset, motor paralysis, ascending in character, without material involvement of sensation, and with loss of the deep and superficial reflexes, with or without involvement of the
Twisted pairs: Does the motor system really care about joint configurations?
Authors: Patrick Haggard, Chris Miall, John Stein
Journal: Behavioral and Brain Sciences (1995)

Abstract Extrapersonal frames of reference for aimed movements are representationally convenient. They may, however, carry associated costs when the movement is executed in terms of the complex coordination of multiple joints they require. Studies that have measured both fingertip and joint paths suggest the motor systems may seek a compromise between simplicity of extrapersonal spatial representation and computational simplicity of multi-joint execution.
Corticosteroids for Severe Community-Acquired Pneumonia
Authors: Richard G. Wunderink
Journal: JAMA (2015)

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Urban Challenges to Psychiatry: The Case History of A Response
Authors: Marshall F. Gilula
Journal: JAMA (1970)

Medical centers often function as though the phrase, "service to the community," belongs only in public health and preventive medicine textbooks. The problems of community mental health programs involve defining the characteristics and needs of a given community, and then devising methods for actual delivery of health care services. This edited volume collates research material from a 12-year study of the Columbia-Washington Heights Community Mental Health Project that began in 1957. The book describes successful attempts to improve mental health services offered by Columbia University's New York State Psychiatric Institute to the surrounding Washington Heights area. Major objectives of this social psychiatric research were to define a specific urban area "in terms of such questions as the prevalence of mental illness and emotional maladjustment, the availability and adequacy of mental health resources, and the attitudes within the community towards mental health and mental health programs." An additional goal was applying
Slow drug infusions using a portable syringe driver.
Authors: B M Wright, K Callan
Journal: BMJ (1979)

no appreciable interstitial smooth muscle proliferation.Electron microscopy showed variable thickening of alveolar septa with a few smooth muscle fibres present between the collagen fibres.Type II pneumocytes were prominent.No foreign material was detected.V. ~~~~~r Area of lung showing collections of desquamated cells, interstitial fibrosis, chronic inflammation, and thick-walled arteries.Haematoxylin and eosin x 100 (original magnification).
THE RELATIONSHIP OF ACNE WITH DANDRUFF AND SEBORRHOEIC DERMATITIS
Authors: E. LIPMAN COHEN.
Journal: British Journal of Dermatology (1945)

Journal Article THE RELATIONSHIP OF ACNE WITH DANDRUFF AND SEBORRHOEIC DERMATITIS Get access E. LIPMAN COHEN. E. LIPMAN COHEN. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 57, Issue 3-4, 1 March 1945, Pages 45–47, https://doi.org/10.1111/j.1365-2133.1945.tb11197.x Published: 01 March 1945
Atrial Septal Defect With Total Anomalous Pulmonary Venous Return in an Adult
Authors: Dong-Ho Shin, Hyo-Eun Park, Sang Il Choi, Kay-Hyun Park, Jung Yun Choi, Goo-Yeong Cho
Journal: Circulation (2011)

A 37-year-old man presented at the emergency depart- ment with recent-onset dyspnea (New York Heart Association functional class IV) and abdominal distention.He had no prior history of exercise intolerance, shortness of breath, cyanosis, or palpitation.In the emergency department, tachycardia and engorged jugular veins were observed, and breath sounds were decreased on the left lower lung field, with no crackles.There was no cardiac murmur.The liver was palpable in the distended abdomen.Chest radiography demonstrated marked cardiomegaly with a snowman appearance of increased pulmonary vascular markings (Figure 1, left).The ECG showed sinus tachycardia with evidence of right ventricular hypertrophy (Figure 1, right).Laboratory tests revealed hypoxia (PaO 2 55.9 mm Hg, Sao 2 89.1%) and elevated levels of N-terminal prohormone of B-type natriuretic peptide (15 125 pg/mL).A computed tomographic angiogram confirmed type I total anomalous pulmonary venous return (supracardiac type; Figure 2, left), with massive thromboembolism of the left pulmonary arteries (Figure 2, right).A transthoracic echocardiogram demonstrated a large atrial septal defect, a dilated and hypertrophied right ventricle compressing the left ventricle with biventricular dysfunction (ejection fraction 34%), loss of drainage of pulmonary venous flow into the left atrium, and large amounts of pericardial effusion (Figure 3 and online-only Data Supplement Movies I through IV).Pulmonary hypertension was suggested from the tricuspid regurgitation flow and inferior vena cava plethora (pulmonary arterial systolic pressure was estimated at 60 mm Hg with the modified Bernoulli equation).The pulmonary veins were traced and
Oral Occupational Parathion Poisoning Treated with 2-PAM Iodide (2-Pyridine Aldoxime Methiodide)
Authors: Griffith E. Quinby, Ted A. Loomis, Harold W. Brown
Journal: New England Journal of Medicine (1963)

OCCUPATIONAL poisonings in agricultural workers caused by organic phosphorus insecticides have become fairly common since the compounds were introduced. These compounds are potent cholinesterase inhibitors and produce symptoms that are due at least partly to this anticholinesterase action.Atropine has long been used in the treatment of intoxication from the organic phosphorus insecticides. It produces its action by pharmacologic blockade of the muscarinic effects of acetylcholine and as such is an incomplete antidote. With the demonstration that organic-phosphate-inhibited cholinesterase can be chemically reactivated by the use of certain hydroxamic acids or aldoxime-type compounds such "reactivator" therapy supplies a theoretically specific . . .