tbuckley/cabot-search huggingface dataset:
Regulation of CXCL16 expression and secretion by myeloid cells is not altered in rheumatoid arthritis
Authors: A W T van Lieshout, R van der Voort, L W J Toonen, S F G van Helden, C G Figdor, P L C M van Riel, T R D J Radstake, G J Adema
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> Chemokine (C-X-C motif) ligand 16 (CXCL16) is secreted by macrophages and dendritic cells (DCs) to attract memory type T cells. CXCL16 expression is increased in arthritic joints of patients with rheumatoid arthritis (RA) and a role for CXCL16 has been suggested in the pathogenesis of RA. To date, little is known about the regulation of CXCL16 on monocytes/macrophages and DCs. The aim of this study was to elucidate how CXCL16 expression is regulated in healthy donors and patients with RA. <h3>Methods:</h3> CD14+cells were isolated from the peripheral blood or synovial fluid of patients with RA and healthy controls, differentiated into different types of dendritic cells or macrophages and stimulated with various cytokines or lipopolysaccharide (LPS). Cell surface proteins, including surface CXCL16, were measured by flow cytometry and soluble CXCL16 was measured by ELISA. <h3>Results:</h3> Distinct types of dendritic cells constitutively express and secrete CXCL16, which is not affected by maturation. Monocytes rapidly upregulate membrane-bound CXCL16 expression and release soluble CXCL16 upon culture. CXCL16 expression by monocytes is transiently inhibited by the Toll-like receptor (TLR)4 ligand LPS. Th2 type cytokines inhibit soluble CXCL16, whereas T helper (Th)1 cell stimulus enhances its release. In RA monocytes/macrophages, neither CXCL16 expression, nor CXCL16 regulation is different from healthy controls. <h3>Conclusions:</h3> Culture of monocytes is the main trigger for CXCL16 surface expression in vitro, which is not altered in RA. Together our data suggest that the increased CXCL16 expression in patients with RA is likely to be caused by increased influx of monocytes rather than intrinsic differences in CXCL16 regulation.
Peripheral Source of MB Band of Creatine Kinase in Alcoholic Rhabdomyolysis
Authors: Arthur J. Siegel
Journal: JAMA (1980)

The MG isoenzyme of creatine kinase (CK MB) was strongly positive in the serum of a patient with alcoholic rhabdomyolysis, and it remained detectable by a standard qualitative assay over a two-year period without clinical or laboratory evidence of myocardial disease. MB isoenzyme was also demonstrated in a homogenate of skeletal muscle. Isoenzyme determinations in serum and tissue were repeated after dilution of toal CK activity to the range optimal for the assay (300 IU/L). Such dilution before isoenzyme separation rendered these samples negative for CK MB. The MB isoenzyme may be detectable in serum from peripheral sources in the presence of high total CK concentrations.
Using Default Options Within the Electronic Health Record to Increase the Prescribing of Generic-Equivalent Medications
Authors: Mitesh S. Patel, Susan Day, Dylan S. Small, John T. Howell, Gillian L. Lautenbach, Eliot H. Nierman, Kevin G. Volpp
Journal: Annals of Internal Medicine (2014)

Low-value services, such as prescribing brand-name medications that have existing generic equivalents, contribute to unnecessary health care spending.To evaluate the association of an intervention by using the electronic health record with provider prescription of generic-equivalent medications.Quasi-experimental study.General internal medicine (IM) (n = 2) and family medicine (FM) (n = 2) clinics at the University of Pennsylvania from June 2011 to September 2012.Attending physicians (IM, n = 38; FM, n = 17) and residents (IM, n = 166; FM, n = 34).In January 2012, the default in the electronic health record was changed for IM providers from displaying brand and generic medications to displaying initially only generics, with the ability to opt out.Monthly prescriptions of brand-name and generic-equivalent β-blockers, statins, and proton-pump inhibitors.During the preintervention period, FM providers had slightly higher rates of generic medication prescribing (range, 80.8% to 85.5%) than did IM providers (range, 75.4% to 79.6%), but both groups had similar trends. In the postintervention period relative to the preintervention period, IM providers had an increase in generic prescribing compared with FM providers for all 3 medications combined (5.4 percentage points [95% CI, 2.2 to 8.7 percentage points]; P < 0.001), β-blockers (10.5 percentage points [CI, 5.8 to 15.2 percentage points]; P < 0.001), and statins (4.0 percentage points [CI, 0.4 to 7.6 percentage points]; P = 0.002). Results for proton-pump inhibitors (2.1 percentage points [CI, -3.7 to 8.0 percentage points]; P = 0.47) were not significant. Subset analyses revealed similar findings for attending physicians. Among residents, however, results were imprecise, with wide CIs.Observational single-center evaluation, comparison groups that represented different specialties, and a small subset of medication classes studied.The use of default options was an effective method to increase the odds of prescribing generic medication equivalents for β-blockers and statins.U.S. Department of Veterans Affairs and Robert Wood Johnson Foundation.
Gene Therapy Restores Vision-Dependent Behavior as Well as Retinal Structure and Function in a Mouse Model of RPE65 Leber Congenital Amaurosis
Authors: Ji-jing Pang, Bo Chang, Ashok Kumar, Steven Nusinowitz, Syed M. Noorwez, Jie Li, Asha Rani, Thomas C. Foster, Vince A. Chiodo, Thomas Doyle, Huashi Li, Ritu Malhotra, Jacqueline T. Teusner, J. Hugh McDowell, Seok-Hong Min, Qiuhong Li, Shalesh Kaushal, William W. Hauswirth
Journal: Molecular Therapy (2005)

Retinal pigment epithelium-specific protein 65 kDa (RPE65) is a protein responsible for isomerization of all-trans-retinaldehyde to its photoactive 11-cis-retinaldehyde and is essential for the visual cycle. RPE65 mutations can cause severe, early onset retinal diseases such as Leber congenital amaurosis (LCA). A naturally occurring rodent model of LCA with a recessive nonsense Rpe65 mutation, the rd12 mouse, displays a profoundly diminished rod electroretinogram (ERG), an absence of 11-cis-retinaldehyde and rhodopsin, an overaccumulation of retinyl esters in retinal pigmented epithelial (RPE) cells, and photoreceptor degeneration. rd12 mice were injected subretinally at postnatal day 14 with rAAV5-CBA-hRPE65 vector. RPE65 expression was found over large areas of RPE soon after treatment. This led to improved rhodopsin levels with ERG signals restored to near normal. Retinyl ester levels were maintained at near normal, and fundus and retinal morphology remained normal. All parameters of restored retinal health remained stable for at least 7 months. The Morris water maze behavioral test was modified to test rod function under very dim light; rd12 mice treated in one eye performed similar to normally sighted C57BL/6J mice, while untreated rd12 mice performed very poorly, demonstrating that gene therapy can restore normal vision-dependent behavior in a congenitally blind animal.
Predicates: External description or neural reality?
Authors: Michael A. Arbib
Journal: Behavioral and Brain Sciences (2003)

Hurford argues that propositions of the form PREDICATE(x) represent conceptual structures that predate language and that can be explicated in terms of neural structure. I disagree, arguing that such predicates are descriptions of limited aspects of brain function, not available as representations in the brain to be exploited in the frog or monkey brain and turned into language in the human.
Preliminary experience with a hybrid nonthoracotomy defibrillating system that includes a biphasic device: Comparison with a standard monophasic device using the same lead system
Authors: Andrea Natale, Jasbir Sra, Kathi Axtell, Cheryl Maglio, Anwer Dhala, Sanjay Deshpande, Mohammad Jazayeri, Abdul Wase, Masood Akhtar
Journal: Journal of the American College of Cardiology (1994)
Mass Accidental Salt Poisoning in Infancy
Authors: Laurence Finberg
Journal: JAMA (1963)

In the first known incidence of a mass salt poisoning of infants, the case fatality rate was 6 of 14 exposed. Five died before the situation was recognized. All five whose brains were examined at autopsy showed hemorrhagic encephalopathy consistent with previous reports of salt poisoning in humans and animals. Eleven of 14 of these infants manifested neurological symptoms. Peritoneal dialysis was attempted in four patients, three of whom survived despite severe illness in two of them. The technique proved feasible under ordinary hospital conditions and may be instrumental in the recovery of patients. Some suggestions for improvement have come from the experience.
Putting the “Art” in “Crash Cart”
Authors: Shana Kusin
Journal: JAMA (2012)

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A gene conversion located 5' to the A gamma gene in linkage disequilibrium with the Bantu haplotype in sickle cell anemia.
Authors: E E Bouhassira, H Lachman, R Krishnamoorthy, D Labie, R L Nagel
Journal: Journal of Clinical Investigation (1989)

Cloning and sequencing of the gamma-globin gene of a sickle cell anemia patient homozygous for the Bantu haplotype has revealed a gene conversion that involves the replacement of an A gamma sequence by a G gamma sequence in the promoter area of the A gamma gene. This event is similar to another gene conversion believed to be responsible for the very high homology between gamma-globin genes, suggesting that the promoter area of these genes is prone to this type of genetic rearrangement. Further analysis demonstrated that the chromosome bearing this gene conversion has a very high frequency among Bantu chromosomes and a very low or nil frequency in other haplotypes linked to the beta s gene. No correlation was found between the G gamma/A gamma ratio and the presence of the gene conversion among Bantu haplotype patients, thus excluding a portion of the gamma gene sequence in the determination of this ratio.
Mycoplasmas in Arthritis and Urethritis
Authors: Hugh H. Hussey
Journal: JAMA (1974)

During the 1930s the idea that a distant focus of infection, possibly streptococcal, held considerable favor as a cause for systemic diseases, notably rheumatoid arthritis. To no avail, many patients sacrificed tonsils and teeth in the cause of physicians who held that view. In the 1940s pleuropneumonia-like organisms (PPLO), now better known as mycoplasmas, came into vogue as possible infectious agents in rheumatoid arthritis and other diseases of unknown etiology. 1,2 Since then, conflicting reports on that subject have appeared.  Mardh et al 3 summarized the results of search by nine author groups for mycoplasmas in the synovial fluid of rheumatoid arthritis (RA) patients and recounted their own experience with 57 patients. In the earlier studies mycoplasmas had been isolated from the joints of RA patients in 95 of 195 cases. However, experiences varied extremely, ranging from 100% success to complete failure of isolation. Mardh et al were able to
The effect of diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: a double-blind, randomized, and placebo-controlled study.
Authors: J Hung, I H Lamb, S J Connolly, K R Jutzy, M L Goris, J S Schroeder
Journal: Circulation (1983)

The effects of oral diltiazem and propranolol, alone and in combination, were compared with those of placebo in 12 patients with stable effort angina.Patients performed symptom-limited, multistage, upright bicycle ergometric exercise while undergoing equilibrium-gated radionuclide an- giographic examination after 2 week periods of 90 mg diltiazem four times daily, 60 mg propranolol four times daily, a combination of 90 mg diltiazem and 60 mg propranolol four times daily, and placebo.All drugs were given double blind and in randomized order.Diltiazem, propranolol, and the combination significantly increased exercise duration compared with placebo (562 + 149, 525 + 115, and 549 121, vs 430 + 132 sec); the drugs also increased time to onset of angina pectoris and ischemic ( 1 mm) ST segment depression (all p < .05).Compared with after placebo, heart rate and rate-pressure product at a fixed submaximal workload were decreased after diltiazem (both p < .05),but were unchanged at peak effort.Heart rate and rate-pressure product at both submaximal and peak effort were decreased by propranolol (all p < .001)and were decreased further by the combination of diltiazem and propranolol (all p < .05vs propranolol).Diltiazem and the combination of diltiazem and propranolol decreased maximal exercise ST segment depression (both p < .01vs placebo).The mean exercise left ventricular ejection fraction was higher in patients on diltiazem than in those on placebo, propranolol, or the combination of diltiazem and propranolol (all p < .05).Adverse side effects severe enough to require dosage reduction (severe sinus bradycardia or orthostatic hypotension) occurred in four patients on combination therapy.High-dose diltiazem alone appears to be as effective as or more effective than moderate-dose propranolol or the combination of diltiazem and propranolol in improving exercise tolerance, myocardial ischemia, and left ventricular function in patients with stable effort angina.Circulation 68, No. 3, 560-567, 1983.CALCIUM-CHANNEL BLOCKERS provide a promising alternative to /8-blockers for the management of patients with exertional angina and fixed coronary ar- tery disease.These drugs can reduce myocardial oxygen demand by decreasing systemic vascular resis- tance, and in some cases cardiac contractility and heart rate, while producing an increase in coronary blood flow through dilation of large coronary vessels. 1 2 The
Chronic myeloid leukemia associated with pure red cell aplasia and terminating in promyelocytic transformation
Authors: Aleksandar Mijovic, Zoran Rolovic, Angelina Novak, Lidija Biljanovic‐Paunovic, Dragica Tomin
Journal: American Journal of Hematology (1989)

After intermittent treatment with busulphan over a 7-year period for chronic myeloid leukemia (CML) in chronic phase, a 39-year-old female developed leukocytosis in association with pure red cell aplasia (PRCA). Bone marrow examination confirmed erythroid aplasia, and culture revealed a total absence of erythroid progenitor cells. The patient then was treated with azathioprine, corticosteroids, cyclophosphamide, plasma exchange, and cyclosporin A, but she remained erythroblastopenic and transfusion dependent for more than a year, at which time a promyelocytic transformation supervened. The authors propose that this sequence of events, hitherto unreported, is a manifestation of the multistep progression of CML.
Use of Glucagon in the Treatment of Pancreatitis
Authors: M. J. Knight, J. R. Condon, R. Smith
Journal: BMJ (1971)

Four patients with pancreatic disease received glucagon intravenously. In two a definite decrease in the volume of pancreatic exocrine secretion was shown, and in one of these pancreatic juice protein and bicarbonate levels also fell. Two patients with acute pancreatitis had pronounced relief of epigastric pain associated with falls in plasma amylase after intravenous glucagon.Several mechanisms could account for the possible beneficial effect of glucagon in pancreatitis, and further studies of its use in this disease are justified.
Please can we have some courageous leadership
Authors: David M Lewis
Journal: BMJ (2007)

<b>1470</b> <h3><b>Objectives</b></h3> Serotonin transporters (SERT) are associated with several neurological and psychiatric disorders including Parkinson’s disease, depression, and schizophrenia. 4-[<sup>18</sup>F]-ADAM (4FADAM) is a SERT tracer with high in-vivo specific binding. Imaging changes in SERT function allows diagnosis, characterization and drug development for brain diseases. Currently published methods for synthesis of 4FADAM are lengthy (&gt;2.5 hours), require 2 reactions, 3 purifications, and give low yields (5-10%). We report a 4FADAM synthesis that reduces synthesis time by more than half and improves chemical yield by over a factor of 5. <h3><b>Methods</b></h3> Optimization: Published reaction, reduction, and HPLC solvents were incompatible, requiring intermediate purification. Labeling and reduction conditions were made compatible and optimized. Acetonitrile, DMF, DMSO, and t-butanol were tested at temperatures of 75-150°C over 30 minutes. Procedure: The precursor (1) was reacted with <sup>18</sup>F-fluoride/K.2.2.2 in dry DMF to give (2). Reduction was accomplished by addition of NaBH<sub>4</sub>-Cu(OAc)<sub>2</sub> without further manipulation. Dilution, filtration, and HPLC purification afforded 4FADAM. <h3><b>Results</b></h3> Radiolabeling yield was 30-50% in DMF, as compared to 5-10% from prior methods in DMSO. The reduction of (2) to 4FADAM went to completion in DMF at 140°C in 20 minutes, eliminating the need for a second reaction vessel or intermediate purification. The product was obtained in &gt;98% radiochemical purity in 90 minutes from end of bombardment. <h3><b>Conclusions</b></h3> Fluorination and reduction of 4FADAM in DMF proceeded quickly and in good yield, eliminating a second reaction vessel and an extraction required in the original published procedures. The overall synthesis time was reduced from 2.5 hours to 90 minutes, while the chemical yield was increased by a factor of more than 5, increasing radiochemical yield by nearly tenfold. The effective specific activity of 4FADAM was greater than 869 GBq (23.5 Ci)/μmol, an improvement factor of 40 compared to prior published values of 22.2MBq (600 mCi)/μmol
ACTIVE SUPPRESSION OF IMMUNOGLOBULIN ALLOTYPE SYNTHESIS
Authors: E. B. Jacobson, Leonore A. Herzenberg, R. Riblet, L. A. Herzenberg
Journal: The Journal of Experimental Medicine (1972)

The mechanism of chronic allotype suppression in (SJL x BALB/c)F1 mice has been investigated by means of cell transfer studies. These mice are phenotypically negative for serum Ig-1b, the paternal allotype determinant on γG2a immunoglubulin, as a result of perinatal exposure to maternal anti-Ig-1b. When spleen or bone marrow (B) cells from suppressed mice were injected into irradiated BALB/c "indicator" hosts, detectable levels of Ig-1b were demonstrated in the sera of a majority of the recipients early after transfer. These results indicate that Ig-1b-producing cells or their precursors are present in the lymphoid tissues of suppressed mice, even though they are not expressed. Within 5–7 wk, it was no longer possible to detect Ig-1b in the sera of these hosts, although cells producing another paternal allotype (Ig-4b) were shown to persist. Control BALB/c mice, injected with spleen and B cells from normal mice, continued to produce high levels of immunoglobulin carrying this allotype. The disappearance of serum, Ig-1b occurred most frequently in the recipients of suppressed spleen cells. Similar results were obtained using a mixture of spleen cells from normal and suppressed mice. Ig-1b production in the recipient mice ceased within a few weeks, even though the majority of cells in the mixture were obtained from normal (nonsuppressed) donors. The data are interpreted as evidence that chronic allotype suppression in mice is actively maintained by cells which are resident in the lymphoid tissues, splenic cells being the most effective. These cells are capable of proliferating in a new host and exerting their suppressive influence on Ig-1b-producing cells and/or their precursors.
Inflammatory Bowel Diseases and Chronic Recurrent Abdominal Pain
Authors: D C A CANDY
Journal: Gut (1999)

Inflammatory Bowel Diseases and Chronic Recurrent Abdominal Pain . Edited by Hadziselimovic F, Herzog B. (Pp 221; illustrated; £66.00.) Dordrecht: Kluwer Academic Publishers, 1997. ISBN 0-7923-8722-8.

I have yet to attend a Falk Symposium but it seems likely to be an agreeable experience. The ability to consider the big questions of biomedical science in a multidisciplinary setting is not to be missed. Perhaps if I write a good review I might be invited to the next one!

Symposium 91 considers two very important gastrointestinal problems which none the less make slightly strange bedfellows. The inside of the dust jacket, but not the cover, revealed that this was a Paediatric Symposium. This was a relief, as I was …
Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency
Authors: Tobias B. Haack, Katharina Danhauser, Birgit Haberberger, Jonathan Hoser, Valentina Strecker, Detlef Boehm, Graziella Uziel, Eleonora Lamantea, Federica Invernizzi, Joanna Poulton, Boris Rolinski, Arcangela Iuso, Saskia Biskup, Thorsten Schmidt, Hans Werner Mewes, Ilka Wittig, Thomas Meitinger, Massimo Zeviani, Holger Prokisch
Journal: Nature Genetics (2010)
Comparison of carbon-11-acetate with fluorine-18-fluorodeoxyglucose for delineating viable myocardium by positron emission tomography
Authors: Rober J. Gropler, Edward M. Geltman, Kondapuram Sampathkumaran, Julio E. Pérez, Kenneth B. Schechtman, Andrea Conversano, Burton E. Sobel, Steven R. Bergmann, Barry A. Siegel
Journal: Journal of the American College of Cardiology (1993)
Prenatal Choice-Reply
Authors: Judy Brown
Journal: JAMA (1990)

<h3>In Reply.—</h3> Ms Blumenthal describes the spectrum of reactions to abnormal prenatal results extremely well. I would also agree with her observation that there may be a reluctance to share the diagnosis itself for fear of an outsider's judgment. A support group is not available in my area, but I have formed a phone network that has been enormously helpful. While the pain of a prenatal "choice" cannot be erased, the sort of help Ms Blumenthal mentions, and more wide-spread awareness of the issues involved, can ease that pain.