tbuckley/cabot-search huggingface dataset:
Expression of Fas and Fas-ligand in primary cutaneous T-cell lymphoma (CTCL): association between lack of Fas expression and aggressive types of CTCL
Authors: O. Zoi-Toli, M.H. Vermeer, E. De Vries, P. Van Beek, C.J.L.M. Meijer, R. Willemze
Journal: British Journal of Dermatology (2000)

Fas (CD95; APO-1) is a transmembrane protein that mediates apoptosis upon cross-linking with Fas-ligand (Fas-L). Interaction of Fas-L expressed by cytotoxic T cells with Fas-expressing tumour cells plays an important part in antitumour immune responses.We aimed to investigate Fas and Fas-L expression in frozen and paraffin-embedded material from a large group of patients with cutaneous T-cell lymphoma (CTCL).Immunostaining with monoclonal antibodies against Fas and Fas-L was performed in material from 23 patients with mycosis fungoides (MF), 10 with lymphomatoid papulosis (LyP), 10 with CD30-positive primary cutaneous large T-cell lymphoma (LTCL) and nine with CD30-negative LTCL. The results were correlated with the type and stage of CTCL and clinical features.Expression of Fas by the large majority of the neoplastic T cells was observed in 15 of 15 cases of plaque-stage MF, 10 of 10 cases of LyP and 10 of 10 cases of CD30-positive LTCL, but only in four of 12 cases of tumour-stage MF and two of nine cases of CD30-negative LTCL. In three of four MF patients in whom both plaques and tumours could be studied, a significant decrease in Fas expression was observed with progression from plaque-stage to tumour-stage disease. Fas-L was expressed by > 50% of the neoplastic T cells in 46 of 56 biopsies, and no clear relationship with type of CTCL and clinical behaviour was observed.This study demonstrates loss of Fas expression in aggressive types of CTCL, but not in indolent types of CTCL. These data suggest that loss of Fas receptor expression may be one of the mechanisms that allow tumour cells to escape an effective immune response, and may contribute to the unfavourable prognosis of some types of CTCL.
Pathogenesis and Treatment of Gallstones
Authors: David E. Johnston, Marshall M. Kaplan
Journal: New England Journal of Medicine (1993)

Gallstones are a major cause of morbidity and mortality throughout the world. In the United States alone, the diagnosis and treatment of gallstone disease accounted for more than $5 billion in direct costs in 1990, including a half million cholecystectomies1. Progress in the understanding and treatment of gallstones has been rapid during the past decade. The decades-long supremacy of open surgical cholecystectomy as therapy for gallstones has been challenged by gallstone-dissolution techniques and shock-wave lithotripsy and has been overthrown by laparoscopic cholecystectomy. This review will summarize current knowledge of the pathogenesis, diagnosis, and treatment of gallstone disease, with emphasis . . .
Good Fences Make Good Neighbors
Authors: Kenneth R. Chien
Journal: Circulation (1999)

Something there is that doesn't love a wall, That sends the frozen-ground-swell under it And spills the upper boulders in the sun, And makes gaps even two can pass abreast.I let my neighbor know beyond the hill, And on a day we meet to walk the line And set the wall between us as we go . . .
Improved Immunogenicity With High-Dose Seasonal Influenza Vaccine in HIV-Infected Persons
Authors: Noah McKittrick
Journal: Annals of Internal Medicine (2013)

HIV-infected persons have less robust antibody responses to influenza vaccines.To compare the immunogenicity of high-dose influenza vaccine with that of standard dosing in HIV-positive participants.Randomized, double-blind, controlled trial. (ClinicalTrials.gov: NCT01262846)The MacGregor Clinic of the Hospital of the University of Pennsylvania, Philadelphia, from 27 October 2010 to 27 March 2011.HIV-infected persons older than 18 years.Participants were randomly assigned to receive either a standard dose (15 mcg of antigen per strain) or a high dose (60 mcg/strain) of the influenza trivalent vaccine.The primary end point was the rate of seroprotection, defined as antibody titers of 1:40 or greater on the hemagglutination inhibition assay 21 to 28 days after vaccination. The primary safety end point was frequency and intensity of adverse events. Secondary end points were seroconversion rate (defined as a greater than 4-fold increase in antibody titers) and the geometric mean antibody titer.195 participants enrolled, and 190 completed the study (93 in the standard-dose group and 97 in the high-dose group). The seroprotection rates after vaccination were higher in the high-dose group for the H1N1 (96% vs. 87%; treatment difference, 9 percentage points [95% CI, 1 to 17 percentage points]; P = 0.029), H3N2 (96% vs. 92%; treatment difference, 3 percentage points [CI, -3 to 10 percentage points]; P = 0.32), and influenza B (91% vs. 80%; treatment difference, 11 percentage points [CI, 1 to 21 percentage points]; P = 0.030) strains. Both vaccines were well-tolerated, with myalgia (19%), malaise (14%), and local pain (10%) the most frequent adverse events.The effectiveness of the vaccine in preventing clinical influenza was not evaluated. The number of participants with CD4 counts less than 0.200 × 109 cells/L was limited.HIV-infected persons reach higher levels of influenza seroprotection if vaccinated with the high-dose trivalent vaccine than with the standard-dose.National Institute of Allergy and Infectious Diseases and Center for AIDS Research of the University of Pennsylvania.
Coronary arteriography before aortic valve replacement.
Authors: F L Rosenfeldt
Journal: BMJ (1979)

given to take away.This is based on triple tetracycline, and after their usual meal times have been discussed with them they are advised on the twice-daily dosage times which will produce least disruption to their usual eating habits.They also receive advice on antacids, milk consumption, iron tablets, and "tonics," in addition to the risks of dental teratogenicity and the necessary continuity of antibiotic regimens.It is my hope that in this manner the poor therapeutic response of NSGI to tetracyclines can be enhanced by intelligent patient co-operation.My comments apply, of course, to the use of tetracyclines in any therapeutic situation.
Abstract 21: Quantitative FRET technology for SUMOylation cascade and high-throughput screening assay for SUMOylation inhibitor in cancer drug discovery
Authors: Jiayu Liao, Hilda Wiryawan, Yang Li, Yang Song, Yan Liu, Jiacong You, Ling Jiang, Harbani Kaur Malik, Amanda N. Saavedra, Sophie Qu
Journal: Cancer Research (2014)

Abstract The ubiquitin–proteasome system and ubiquitin-like protein pathways, such as SUMOylation, are critical in protein homeostasis and activities in vivo and are emerging as a new strategy to treat many acute and chronic human diseases, such as cancers. Although various kinase inhibitors have been developed as target-based therapy, solid tumors are still challenges in clinical therapy because various resistant are developed after kinase inhibitor treatments, and therapeutic agents with novel mechanisms are urgently needed. SUMO has been shown to modify various critical proteins, such as p53, MDM2, Estrogen receptor and androgen receptors. More recently, a genome-wide siRNA screening shown that inhibition of SUMO E1 ligases can lead to synergistically lethality of c-Myc overexpressed breast cancer cells. However, so far, specific inhibitor of SUMOylation is still not available for the community. Fig. 1. SUMOylation in human diseases and quantitative systems biology approach for basic and translational research of SUMOylation. We developed a novel quantitative Förster resonance energy transfer (FRET) technology platform for both basic kinetics parameter determinations and high-through screening(HTS) assays for SUMOylation cascade. The novel theoretical and experimental procedures for protein interactions affinity(Kd) determinations in the SUMOylation cascade, including the interaction between SUMO1 and its E2 ligase, Ubc9, E1 heterodimers(Aos1 and Uba2), E1 and E2 interactions(Uba2 and Ubc9), and E2 and substrate interactions(Ubc9 and RanGap1c) and protease kinetics, Kcat/KM of SENP1 endopeptidase activity have been developed in a systems biology manner. The data are in good agreement with traditional methods. Multiple FRET-based HTS assays have also been developed and HTS campaigns have led to very promising hit that can preferentially kill Non-small cell lung cancer cells. The novel SUMOylation inhibitor can be used for cancer treatments by synergistically lethality strategy. Citation Format: Jiayu Liao, Hilda Wiryawan, Yang Li, Yang Song, Yan Liu, Jiacong You, Ling Jiang, Harbani Kaur Malik, Amanda N. Saavedra, Sophie Qu. Quantitative FRET technology for SUMOylation cascade and high-throughput screening assay for SUMOylation inhibitor in cancer drug discovery. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 21. doi:10.1158/1538-7445.CANSUSC14-21
Intolerance to Ethanol
Authors: Michael C. Gordon
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Dr Hussey's editorial concerning "Indians' Intolerance to Ethanol" (235:1596, 1976) attracted my attention. In the editorial he relates the story of a physician who regularly drank a six-pack of beer daily, but who switched to Scotch because he was getting fat. Drunkenness and occasional belligerence followed, which was attributed to the physician's unfamiliarity with Scotch whiskey. A much more likely explanation is that the change from beer to Scotch was a step in the progression of alcoholism, and that the idea of reducing caloric intake was a rationalization. As the disease of alcoholism progresses, the victim unwittingly loses control of his drinking, and unplanned drunkenness results. In the case cited, the diagnosis could be established by the physician's attempting to return to controlled drinking. In most cases, with a concerted effort, most alcoholics at this stage will succeed in "cutting down" for a period of time. However,
Hodgkin's Disease and Infectious Mononucleosis: Is There a Causal Association?
Authors: M. J. Lacher
Journal: CA A Cancer Journal for Clinicians (1981)

Hodgkin's disease, the authors concluded that persons at relatively high risk for the disease during young adulthood are those who as children belonged to small fami lies, lived in single-family homes, had rel atively few neighborhood playmates, and had relatively well-educated parents.They were more likely to be Jewish and to have a history of infectious mononucleosis.On the other side of the world, Cohen and Hamilton2 studied the epidemiologic and histologic patterns of Hodgkin's dis ease among the black and white popula tions of Johannesburg, South Africa, com paring 88 black patients and 54 white patients diagnosed over the four-year pe riod from 1971 to 1974.They did not em phasize any potential viral etiology, but they did note that with respect to histology and age and sex distribution, their data strengthened â€oe¿ the existing general hypoth esis that host immune capacity, influenced by socioeconomic factors, may have a strong and measurable effect on the patho genesis of Hodgkin's disease.â€•No refer ence was made to infectious mononucleo sis.Cohen and Hamilton did place much emphasis on differences in histologic pat terns of Hodgkin's disease (lymphocyte predominant, nodular sclerosis, mixed cel lularity, and lymphocyte depleted types) as well as differences in age-specific in cidence curves.They noted, for instance, the similarity between white Johannesburg patients, and black patients in the United
Hepatic Tumor Necrosis Factor Signaling and Nuclear Factor-κB: Effects on Liver Homeostasis and Beyond
Authors: Andy Wullaert, Geert van Loo, Karen Heyninck, Rudi Beyaert
Journal: Endocrine Reviews (2007)

The proinflammatory cytokine TNF has a pivotal role in liver pathophysiology because it holds the capacity to induce both hepatocyte cell death and hepatocyte proliferation. This dual effect of TNF on hepatocytes reflects its ability to induce both nuclear factor κB (NF-κB)-dependent gene expression and cell death. Multiple studies have demonstrated the crucial role of the transcription factor NF-κB in the decision between life and death of a hepatocyte. Massive hepatocyte apoptosis preceding embryonic lethality in NF-κB-deficient mice constituted the first indication of an essential antiapoptotic function of NF-κB in the liver. Although many studies confirmed this crucial cytoprotective role of NF-κB in adult liver, a number of genetic studies recently obtained conflicting results on the exact role of NF-κB in different mouse models of TNF hepatotoxicity, demonstrating that caution should be taken when interpreting studies using different NF-κB-deficient mice in distinct models of liver injury. Recent reports showing a role for hepatic NF-κB activation in the proliferation of malignant cells during hepatocarcinogenesis, and in the progression of fatty liver diseases to insulin resistance and type 2 diabetes mellitus demonstrate that NF-κB can also have more detrimental effects in the liver. Moreover, its role in the development of the metabolic syndrome emphasizes that hepatic NF-κB activation might also have adverse effects on the endocrine system. Therefore, understanding the regulation of hepatic TNF signaling and NF-κB activation is of critical therapeutic importance. In this review, we summarize how studies on the role of NF-κB in different mouse models of liver pathologies have contributed to this understanding.
Can infection be abolished?
Authors: N. R Grist
Journal: BMJ (1983)

serotype 3, biotype 4, has been isolated several times from patients, food handlers,2 pigs, and monkeys.3Other serotypes or biotypes of Y enterocolitica, which are ubiquitous soil and water saprophytes,4 are probably as frequent in the tropics as they are in the temperate zone.Recently, a biotype 1 strain of Y enterocolitica, isolated from the stools of an African, was submitted to our laboratory by Dr J Bogaerts from Kigali (Rwanda).
Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma
Authors: Philippe Moreau, Frédéric Garban, Michel Attal, Mauricette Michallet, Gérald Marit, Cyrille Hulin, Lotfi Benboubker, Chantal Doyen, Mohamad Mohty, Ibrahim Yakoub-Agha, Serge Leyvraz, Philippe Casassus, Hervé Avet-Loiseau, Laurent Garderet, Claire Mathiot, Jean-Luc Harousseau
Journal: Blood (2008)
Letter: Ruptured aneurysm of splenic artery in pregnancy.
Authors: D Gibbens, D Heath
Journal: BMJ (1974)

different (t = 163, P = 0 20) and breast and bottle feeding were equally distributed between the two groups x2 = 0 054; N.S.).Though the mean duration of infusion of oxytocin in group 1 (10-8 ± 8-7 hr) was greater than in group 2 (8 0 ± 7-1 hr) the difference was not statistically significant (t = 1 49, P = 0-14).We agree with Dr. B. Alderman and Professor J. M. Beazley (7 September, p. 624) that the first and sixth days are not ideal times to detect peak neonatal bilirubin levels.However, as we pointed out in our paper, the sixth day was a time at which blood was already being taken routinely for amino-acid screening and this timing of samples avoided exposing the infants to additional blood-letting.Though the re- corded peak values in our data may be lower for this reason, any increase in neonatal hyperbilirubinaemia should still be reflected in a higher mean value on the sixth day.-We are, etc.,
Preventing the spread of MRSA: …the epidemiological nature of the problem should be tackled…
Authors: Nicholas Akerman
Journal: BMJ (2004)

EDITOR—The attitude towards methicillin resistant Staphylococus aureus (MRSA) in the United Kingdom is a case of shutting the gate after the horse has bolted. Voss says that in Scandinavia and the Netherlands, where the prevalence of MRSA is low, a screening and decolonisation …
Malignant Gout with Tophaceous Small Intestine and Megaloblastic Anaemia
Authors: C.F. Hawkins, H.A. Ellis, Annette Rawson
Journal: Annals of the Rheumatic Diseases (1965)

Gout, like diabetes, is worst in youth.Often impossible to control by uricosuiric drugs, it may cause premature death.Such was the case of a man described by Kersley, Mandel, and Jeffrey (1950).He developed gout at 18 years, became crippled at 21, and died at 24 from bronchopneumonia, associated with a tophus in the atlas vertebra.His brother, who came under our care, also developed gout at 18 years, and pursued a similar course (Fig. 1), though he survived until age 32, when he died from renal failure.This patient too showed many features of interest.Case Report Attacks of pain in the big toe joint began at 18 years, and usually started during the night.All joints soon became involved and at 20 years there were typical radio- logical changes in the bones.At 21 years, many large tophi had developed, with numerous discharging areas around severely deformed joints.The serum uric acid was 16 mg.per cent.At 24 the patient was crippled- a tall, thin, pale man, walking with difficulty.His weight had fallen rapidly from 70 to 50 kg.He was 1 * 8 metres (6 ft) tall.Typical tophi were present on the ears.All fingers were affected, with tophaceous deposits varying in size up to 3 cm. in diameter, and numerous discharging sinuses.Both elbows were gouty.There was stiffness of the shoulders and effusions into both knee joints.Renal damage was then discovered; the urine contained protein, red cells, and casts, and the creatinine clearance was 19 ml. per min., though the serum urea was normal (24 mg./100 ml.).The Congo red test for amyloidosis was negative.The cardiovascular system, including the blood pressure (120/70 mm.Hg), was normal.The pallor was due to a macrocytic anaemia, haemoglobin 9 9 g. per 100 ml. (68per cent.);red blood cells 2,870,000/mm.3,colour index 1 19; white blood cells 12,700/mm.3,with a normal differential count; platelets
NUTRITIONAL IRON-DEFICIENCY ANAEMIA: WITH SPECIAL REFERENCE TO PREVALENCE AND AGE AND SEX INCIDENCE
Authors: L. S. P. Davidson, H. W. Fullerton, R. M. Campbell
Journal: BMJ (1935)

During the past four years a large-scale investigation into the aetiology and treatment of iron-deficiency anaemias has been carried out by a team of workers in Aberdeen.
Complications in Anesthesiology
Authors: James E. Cottrell
Journal: JAMA (1983)

Complications in Anesthesiology is a substantial, even copious, contribution to anesthesia literature. Its 62 authors have written 57 chapters covering 13 major topics in 765 largeformat pages. Although some space is devoted to relatively minor details about rare occurrences, the redundancy that often plagues multiauthored compendiums is almost absent. Because anesthesia alters vital homeostatic mechanisms and can be highly invasive, the potential for complications is great. Indeed, watching for and dealing with complications is the mainstay of clinical practice. This volume covers in detail the whole spectrum of problems that might be encountered—from human error to equipment failure. Completeness makes the book both a text and a reference, so it should be of value to residents, clinicians, and academicians involved with anesthetic care ranging from the emergency room to outpatient management of chronic pain.  The editors are to be commended for including chapters on awareness during anesthesia and postoperative emotional
New York's road to health
Authors: K. McColl
Journal: BMJ (2008)

Alterations in the PIK3CA and PTEN genes were assessed in 40 prostate tumors (radical prostatectomy samples). Genetic analyses in glands of the highest Gleason pattern within each tumor revealed PIK3CA amplification in 13%, PIK3CA mutations in 3%, PTEN homozygous deletion in 13% and PTEN hemizygous deletion in 8% of the cases analyzed. Supporting the view that PTEN and PIK3CA act in the same PI3K signaling pathway, genetic alterations in the PIK3CA and PTEN genes were mutually exclusive, except in one tumor. Overall, 13 of the 40 (33%) prostate tumors had alterations in the PI3K pathway. For cases with genetic alterations, other tumor areas with lower Gleason patterns as well as non-tumorous prostate glands were also analyzed. Of nine tumors with Gleason score 7, five cases contained the same genetic alterations in tumor areas of Gleason patterns 3 and 4, whereas in another four cases, genetic alterations were detected only in tumor areas of Gleason 4 but not Gleason 3 patterns. There were no alterations in non-tumorous glands. These results suggest that genetic alterations in the PI3K pathway are common in prostate cancer, and occur mainly through PIK3CA amplification and PTEN hemizygous or homozygous deletion. Glands of Gleason pattern 3 are genetically heterogeneous, some containing the same genetic alterations observed in glands of Gleason pattern 4.
Cellular Immune Deficiency in Two Siblings with Hereditary Orotic Aciduria
Authors: Robert Girot, Michèle Hamet, Jean-Louis Perignon, Michel Guesnu, Richard M. Fox, Pierre Cartier, Anne Durandy, Claude Griscelli
Journal: New England Journal of Medicine (1983)

HEREDITARY orotic aciduria is a rare inborn error of pyrimidine metabolism that is associated with autosomal recessive inheritance.1 The disease is usually characterized by retarded growth and development, anemia, and megaloblastic bone marrow. To date, only nine patients with this disease have been described.2 3 4 5 6 7 8 9 10 The enzymatic defect involves either two sequential enzymes of de novo pyrimidine biosynthesis (orotate phosphoribosyltransferase [OPRT, EC 2.4.2.10.] and orotidine-5′-phosphate decarboxylase [ODC, EC 4.1.1.23.]), in the Type I form of the disease, or, as described by Fox et al.,8 only one of these enzymes (ODC), in the Type II form. Replacement therapy with uridine usually leads . . .
There is no evidence base for proposed dementia screening
Authors: M. D. Brunet, M. McCartney, I. Heath, J. Tomlinson, P. Gordon, J. Cosgrove, P. Deveson, S. Gordon, S.-A. Marciano, D. Colvin, M. Sayer, R. Silverman, N. Bhattia
Journal: BMJ (2012)

<h3>Abstract</h3> A computational framework combining Agent-Based Models (ABMs) and Deep Learning techniques was developed to help design microbial communities that convert light and CO<sub>2</sub> into useful bioproducts. An ABM that accounts for CO<sub>2</sub>, light, sucrose export rate and cell-to-cell mechanical interactions was used to investigate the growth of an engineered sucrose-exporting strain of <i>Synechococcus elongatus</i> PCC 7942. The ABM simulations produced population curves and synthetic images of colony growth. The curves and the images were analyzed, and growth was correlated to nutrients availability and colonies' initial spatial distribution. To speed up the ABM simulations, a metamodel based on a Recurrent Neural Network, RNN, was trained on the synthetic images of growth. This metamodel successfully reproduced the population curves and the images of growth at a lower computational cost. The computational framework presented here paves the road towards designing microbial communities containing sucrose-exporting <i>Synechococcus elongatus</i> PCC 7942 by exploring the solution space <i>in silico</i> first.
The Role of Vessel Tone in Maintaining Pulmonary Vascular Resistance in Patients with Mitral Stenosis
Authors: HERBERT J. SEMLER, JOHN T. SHEPHERD, EARL H. WOOD
Journal: Circulation (1959)

Changes in pulmonary vascular (arteriolar) resistance were estimated in 58 patients with mitral stenosis following mitral valvotomy and during exercise. Evidence is presented that changes in "resistance" reflect active changes in the caliber of the vessels due to alteration in their smooth muscle tone, valvotomy being followed by a decrease in tone and exercise by an increase.