tbuckley/cabot-search huggingface dataset:
IL-33–Responsive Innate Lymphoid Cells Are an Important Source of IL-13 in Chronic Rhinosinusitis with Nasal Polyps
Authors: Joanne L. Shaw, Samer Fakhri, Martin J. Citardi, Paul C. Porter, David B. Corry, Farrah Kheradmand, Yong-Jun Liu, Amber Luong
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined.The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS.Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining.Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract.These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.
Age-dependent HLA genetic heterogeneity of type 1 insulin-dependent diabetes mellitus.
Authors: S Caillat-Zucman, H J Garchon, J Timsit, R Assan, C Boitard, I Djilali-Saiah, P Bougnères, J F Bach
Journal: Journal of Clinical Investigation (1992)

The association of insulin-dependent diabetes mellitus (IDDM) with certain HLA alleles is well documented in pediatric patients. Whether a similar association is found in adult-on-set IDDM is not clear, although the disease occurs after the age of 20 in 50% of cases. HLA class II DRB1, DQA1, and DQB1 alleles were studied in 402 type I diabetics and 405 healthy controls (all Caucasian) using oligonucleotide typing after gene amplification. Alleles DRB1*03, DRB1*04, DQB1*0201, DQB1*0302, DQA1*0301, and DQA1*0501 were indeed enriched in diabetics and the highest relative risk was observed in patients carrying both the DRB1*03-DQB1*0201 and the DRB1*0402 or DRB1*0405-DQB1*0302 haplotypes. However none of these alleles, or specific residues, could alone account for the susceptibility to IDDM. Furthermore, there were major differences in HLA class II gene profiles according to the age of onset. Patients with onset after 15 yr (n = 290) showed a significantly higher percentage of non-DR3/non-DR4 genotypes than those with childhood onset (n = 112) and a lower percentage of DR3/4 genotypes. These non-DR3/non-DR4 patients, although presenting clinically as IDDM type 1 patients, showed a lower frequency of islet cell antibodies at diagnosis and a significantly milder initial insulin deficiency. These subjects probably represent a particular subset of IDDM patients in whom frequency increases with age. The data confirm the genetic heterogeneity of IDDM and call for caution in extrapolating to adult patients the genetic concepts derived from childhood IDDM.
An Analysis of Twenty-Four Cases of Enteric Fever in Children
Authors: J. P. Wightman
Journal: BMJ (1894)

These extended to the valve, beyond wlichl only one or two pieces of tin foil were found.At the inquest it appeared from the evidence of the deputy of the lodging house whlere hie lhad resided ofl' and oIn for three years, that lhe was il the lhabit of wagering to eat the plate his food was on, and then proceed to do so.He was also said to lhave eaten bottles and otlher articles.He was not known to lhave done so recently.REMARsS.--The obstruction appeared to lhave been deter- mined by the string and cotton becoming entangled around the corks, wlichl were closely wedged togetlher, and close to them eight of the nine copper coins were piled one upon anothier.The lower of the hooks attached to the piece of
Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity
Authors: Erdogan Taskesen, Lars Bullinger, Andrea Corbacioglu, Mathijs A. Sanders, Claudia A. J. Erpelinck, Bas J. Wouters, Sonja C. van der Poel-van de Luytgaarde, Frederik Damm, Jürgen Krauter, Arnold Ganser, Richard F. Schlenk, Bob Löwenberg, Ruud Delwel, Hartmut Döhner, Peter J. M. Valk, Konstanze Döhner
Journal: Blood (2010)
Evaluating mass training in cardiopulmonary resuscitation.
Authors: A Raffle
Journal: BMJ (1987)

jogging or brisk walking three times a week), yet only 15% of the population of the United Kingdom do this.The real benefits of exercise have not yet been emphasised, either by this campaign or by previous attempts, and the few hazards of exercise have been overemphasised.Mass screening and drug treatment are costly, exercise is cheap, and all that is required is a positive attitude by health authority managers and general practitioners.For these reasons and the financial state of the NHS exercise deserves a higher priority.
Hyperferritinemia and iron overload in type 1 Gaucher disease
Authors: Philip Stein, Hannah Yu, Dhanpat Jain, Pramod K. Mistry
Journal: American Journal of Hematology (2010)

Hyperferritinemia occurs in Gaucher disease but its clinical spectrum or its association with systemic iron overload and HFE mutations are not known. In 114 patients with Type 1 Gaucher disease, we determined serum ferritin, transferrin saturation and HFE genotype. The results were correlated with the extent of hepatosplenomegaly, overall Gaucher disease severity score index, and response to enzyme replacement therapy. In a subset of patients with radiological and/or laboratory evidence of systemic iron overload, liver biopsy was performed. There was a mean 3.7-fold elevation of serum ferritin over the upper limit of normal (ULN). Prior splenectomy was associated with most severe hyperferritinemia compared to patients with intact spleen (6.53 x ULN vs. 2.69 x ULN, P = 0.003). HFE genotyping revealed two patients homozygous for H63D mutation and 30% of patients heterozygote carriers of H63D mutation; no patients harbored C282Y mutation; there was no correlation of ferritin with HFE genotype. Ferritin level correlated with liver volume (Pearson correlation coefficient = 0.254, P = 0.035) and it was negatively correlated with hemoglobin (r = -0.315, P = 0.004); there was no relationship with other indicators of Gaucher disease activity. Enzyme replacement therapy (ERT) resulted in amelioration of hyperferritinemia: 707 +/- 898 ng/ml vs. 301 +/- 310 ng/ml (P = 0.001), transferrin saturation remained normal. Three patients were suspected of clinical iron overload, confirmed on liver biopsy. Iron accumulation was variably noted in hepatocytes and Kupffer cells. There is a high prevalence of hyperferritinemia in Type 1 Gaucher disease that is associated with indicators of disease severity, reversed by ERT and is not related to HFE mutations.
Connexins protect mouse pancreatic β cells against apoptosis
Authors: Philippe Klee, Florent Allagnat, Helena Pontes, Manon Cederroth, Anne Charollais, Dorothée Caille, Aurore Britan, Jacques-Antoine Haefliger, Paolo Meda
Journal: Journal of Clinical Investigation (2011)

Type 1 diabetes develops when most insulin-producing β cells of the pancreas are killed by an autoimmune attack. The in vivo conditions modulating the sensitivity and resistance of β cells to this attack remain largely obscure. Here, we show that connexin 36 (Cx36), a trans-membrane protein that forms gap junctions between β cells in the pancreatic islets, protects mouse β cells against both cytotoxic drugs and cytokines that prevail in the islet environment at the onset of type 1 diabetes. We documented that this protection was at least partially dependent on intercellular communication, which Cx36 and other types of connexin channels establish within pancreatic islets. We further found that proinflammatory cytokines decreased expression of Cx36 and that experimental reduction or augmentation of Cx36 levels increased or decreased β cell apoptosis, respectively. Thus, we conclude that Cx36 is central to β cell protection from toxic insults.
A new model of shouldered survival curves.
Authors: S Kumazawa
Journal: Environmental Health Perspectives (1994)

Recently, the linear-quadratic equation has been used to construct the dose-response relationships of ionizing radiation. The radiobiological theory on which this relationship is based indicates that at low doses, the risk of a biological lesion being formed should depend linearly on dose if a single event is required or quadratically on dose if two events are required. The same approach has also been used to construct the shouldered survival curves, which indicate a lower response of cell killing at low doses of low linear energy transfer (LET) radiation than at high doses because of repair. However, a different approach is possible, derived from the concept of generating the hybrid lognormal distribution, in which the hybrid form of linear and logarithmic components of a random variable is used. The hybrid form is a formulation of the phenomenon in which there is a feedback mechanism against the large change in the random variable. This paper presents a new model of shouldered survival curves, called a hybrid scale model, which has two parameters: the inactivation constant and the protective factor. In the model, the surviving fraction, normalized by a protective factor plotted in a hybrid scale, is assumed to be linear against the dose. This simple model provides an implication of the shoulder of survival curve and the effect of recovery time of radiation damage, as well as giving a good to the well-known data of split-dose experiments with mammalian cells.
Abstract LB-98: Transcriptomic and genomic landscape of ovarian cancer stem cells
Authors: Ahmet Zehir, Server A. Ertem, Malcolm A.S. Moore
Journal: Cancer Research (2012)

Abstract Ovarian cancer (OvCa) is the fifth leading cause of death among woman in USA. OvCa remains a fatal disease because of the lack of accurate early diagnostic methods as well as the heterogeneous nature of the disease itself. The cancer stem cell (CSC) hypothesis states the existence of a sub-population of cells in tumors that has the ability to self-renew as well as generating a fully differentiated tumor tissue. CSCs are also postulated to be resistant to conventional therapies, which might explain the recurrent nature of many cancers. We have recently identified a novel cellular structure in the ascites of NOD/SCID mice engrafted intraperitoneally with an OvCa cell line, consisting of free-floating chains of 4-72 cells with an extensive pericellular glycocalyx. We termed these structures “catenae” (Latin for “chains”). Catena develop by symmetric self-renewal and each cell retain tumor initiating function when transplanted in NOD/SCID IL2Rγ null mice. To elucidate the transcriptomic terrain and analyze expression of known and novel biomarkers, we performed RNA sequencing of catena using the SOLiD platform. We obtained more than 110 Million single reads of which ∼ 60% mapped uniquely to the human genome. Using this powerful technology, we detected expression of 15494 genes with RPKM values higher than 0.3 for which there are 42931 alternatively spliced transcripts. Roughly 3.5% of these alternative-splicing events seem to be novel. By using the aligned reads we detected 14361 single nucleotide polymorphisms (SNPs) which, after filtering, lead to 199 genes with novel SNPs. We also used the cancer genome atlas (TCGA) public database to determine whether any of these SNPs might be responsible for fast recurrence of ovarian cancer or shorter life span of patients. Furthermore, we detected novel fusion genes, which might lead to molecular classifications in ovarian CSCs. Once validated, these SNPs and fusion genes might prove to be pharmaceutical targets for eradication of ovarian cancer or improving patients’ lives. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-98. doi:1538-7445.AM2012-LB-98
The Dll4/Notch pathway controls postangiogenic blood vessel remodeling and regression by modulating vasoconstriction and blood flow
Authors: Ivan B. Lobov, Eunice Cheung, Rajeev Wudali, Jingtai Cao, Gabor Halasz, Yi Wei, Aris Economides, Hsin C. Lin, Nicholas Papadopoulos, George D. Yancopoulos, Stanley J. Wiegand
Journal: Blood (2011)
Link with bowel disease fuels controversy over vaccine
Authors: H. Bower
Journal: BMJ (1998)

Doctors at the Royal Free Hospital in London believe they have uncovered a new bowel disease in children that may be linked to autism and triggered by the measles, mumps, and rubella vaccine (MMR). The claim follows controversial work from the same team suggesting a causal link between measles vaccination and inflammatory bowel disease.

The report stems from the investigation of 12 children aged between 3 and 10 years who were consecutively referred to the department of paediatric gastroenterology at the Royal Free Hospital ( Lancet 1998;351:637-41). After a period of apparently normal development, the children had lost acquired skills, including language, and had developed gastrointestinal symptoms such as diarrhoea, abdominal pain, and bloating.

All 12 were found to have lumpy swellings of the lymph nodes and patchy recurring inflammation in the intestine. In nine of the children autism had also been diagnosed, and in eight children the parents or the …
THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE
Authors: Edward B. Krumbhaar, John H. Musser, Richard M. Pearce
Journal: The Journal of Experimental Medicine (1913)

In the splenectornized dog the anemia caused by hemolytic poisons (hemolytic immune serum and sodium oleate) and by bleeding is of a severer grade, runs a longer course, and is accompanied by a less rapid regeneration of the blood than is the case in the normal dog. Also in the splenectomized dog, especially after the use of hemolytic serum, the leucocytosis is greater than in the normal animal. The splenectomized dog almost uniformly exhibits an increased resistance of the red cells to hypotonic salt solution, but after the administration of hemolytic poisons, and especially hemolytic serum, this increased resistance disappears and a decreased resistance persists for long periods of time. The same change occurs in the normal dog, but in the latter the return to the previous degree of resistance is more rapid than in the splenectomized animal.
Points from Letters: Upgrading V.D. Departments
Authors: A. Grimble
Journal: BMJ (1970)

BITISH(often in his prime) rather than take the risk of a breakdown in health in the sub- sequent five years.Compare the lot of the man who gets an award, say, at 50.Not only can he afford to ease off earlier, he can also spare the time to attend clinical meetings, administrative committees, and write papers, and in due course this bears the fruit of an even higher award.Although the system is supposedly
Novel mucosal immunization with polysaccharide–protein conjugates entrapped in alginate microspheres
Authors: Nam-Hyuk Cho, Seung-Yong Seong, Kyung-Hee Chun, Yong-Hee Kim, Ick Chan Kwon, Byung-Yoon Ahn, Seo Young Jeong
Journal: Journal of Controlled Release (1998)
INFLUENCE OF CT AND CS-137 ATTENUATION CORRECTION ON FDG-PET SUV
Authors: S Mahadeo, S Jana, D Milstein, S Heller, C Isasi, M D. Blaufox
Journal: Clinical Nuclear Medicine (2005)

Greater New York and New England Chapters, the Society of Nuclear Medicine 18th Annual Northeast Regional Scientific Session Abstracts October 22–October 24, 2004—Stamford, Connecticut: PDF Only
Experimental atrial septal defect closure with a new, transcatheter, self-centering device.
Authors: G S Das, G Voss, G Jarvis, K Wyche, R Gunther, R F Wilson
Journal: Circulation (1993)

BACKGROUND Despite two decades of research, a transcatheter atrial septal defect closure device is not available for clinical use. We have designed a new superelastic Nitinol-Dacron, double-disk, self-centering, atrial septal defect closure device and studied its efficacy in a canine model of atrial septal defects. METHODS AND RESULTS Atrial septal defects were created surgically in 20 adult dogs using either a 7.5-mm or 10-mm punch. Percutaneous transcatheter closures were attempted using a new device. The device sizes used were 20 mm in 6 dogs, 22 mm in 9, and 25 mm in 5 (22.1 +/- 1.9 mm, mean +/- SD). The stretched atrial septal defect diameter was 10.5 +/- 1.3 mm, and the device to stretched atrial septal defect diameter ratio was 2.1 +/- 0.3. Closures were successful in 19 studies and unsuccessful in 1. Angiography showed a left-to-right shunt in all 20 dogs before closure. Immediately after closure (n = 19), there were no shunts in 17 and trivial shunts in 2. Six dogs were followed for a period of 4.7 +/- 3.0 months (range, 2 to 8 months). The trivial shunt present in 1 animal immediately after closure had closed by the time of the repeat study. Spontaneous embolization of the device was not seen during follow-up. A solitary wire fracture was found 8 months after closure in 1 device. Light microscopy at 8 weeks in 3 dogs showed the devices to be covered by smooth endocardium, enmeshed in mature collagen tissue, with a minimal mononuclear cell infiltration. Retrievability was assessed by deliberately embolizing 4 devices in 2 dogs into the right atrium (n = 1) and pulmonary artery (n = 3). All devices were successfully retrieved with a snare. CONCLUSIONS This feasibility study demonstrates that this new self-centering atrial septal defect closure device has a number of design features that permit effective and safe closures in a canine model. These results support the investigation of this device in human clinical trials.
Methadone Treatment and Acquired Immunodeficiency Syndrome
Authors: Paul M. D'Amico
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Dr Dole<sup>1</sup>implies that there are no reasonable medical arguments against the methadone program. Methadone is an opiate on the supply side and it is medically irrelevant whether it is legal or illegal. The use of a psychoactive drug that creates drug dependence (a disease) in a "treatment plan" is contorted thinking. Perpetrators of this system are "iatrogenic enablers"; this is a real medical problem. The medical profession itself is bankrupt if it promotes distribution of a class I synthetic opiate under the guise of treatment. To promote enslavement to any psychodrug is morally reprehensible and unacceptable as either medical or public policy. Although some victims receiving methadone maintain their dosages, the majority need higher and higher dosages owing to tolerance, with eventual "copping on the street." Illegal diversion is a major problem—anyone can get "street methadone" in the cities. Methadone centers are marketplaces for all
New studies confirm MAO inhibitors' efficacy in treating severe anxiety
Authors: E. R. Gonzalez
Journal: JAMA (1981)

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Training and Finances Of the GP
Authors: HENRY BACHMAN
Journal: JAMA (1966)

To the Editor:  I am sure that all the facts, such as changes in educational standards, prestige, etc, are of importance ( 197 :985, 1966). However, as a country physician, I would like to bring out the following pertinent facts.   Premedical education in general is satisfactory. With some reasonable postgraduate effort, the general practitioner is and remains well equipped for general practice, family counseling, and whatever may be expected from a family physician.  The general practitioner usually has top prestige in his community, possibly exceeding that of the specialist. There has been lack of social, educational and religious facilities in some rural areas, but in this day and age of ever faster communications, distance and time have become less important.   In your appraisal of the situation and in many others, I miss the question of dollars and cents. The pay for interns and residents in this socially conscious and
P653 RECLASSIFICATION OF IMMUNOTOLERANT CHRONIC HEPATITIS B INFECTION; DETECTION OF HBV VARIANTS WITH IMPLICATIONS FOR HBV DNA, HBsAg AND HBeAg LEVELS
Authors: G. Rosenberg, J. Bayliss, A. Gaggar, K. Kitrinos, M. Subramanian, E. Gane, H.L. Chan, R. Hammond, S. Bowden, P. Revill, S. Locarnini, A. Thompson
Journal: Journal of Hepatology (2014)
Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.
Authors: K S Nair, S L Welle, D Halliday, R G Campbell
Journal: Journal of Clinical Investigation (1988)

Because intravenous infusion of beta-hydroxybutyrate (beta-OHB) has been reported to decrease urinary nitrogen excretion, we investigated in vivo metabolism of leucine, an essential amino acid, using L-[1-13C]leucine as a tracer during beta-OHB infusion. Leucine flux during beta-OHB infusion did not differ from leucine flux during normal saline infusion in nine normal subjects, whereas leucine oxidation decreased 18-41% (mean = 30%) from 18.1 +/- 1.1 mumol.kg-1.h-1 (P less than 0.01), and incorporation of leucine into skeletal muscle protein increased 5-17% (mean = 10%) from 0.048 + 0.003%/h (P less than 0.02). Since blood pH during beta-OHB infusion was higher than the pH during saline infusion, we performed separate experiments to study the effect of increased blood pH on leucine kinetics by infusing sodium bicarbonate intravenously. Blood pH during sodium bicarbonate infusion was similar to that observed during the beta-OHB infusion, but bicarbonate infusion had no effect on leucine flux or leucine oxidation. We conclude that beta-OHB decreases leucine oxidation and promotes protein synthesis in human beings.