tbuckley/cabot-search huggingface dataset:
Re: Indeterminate 1-2 cm nodules found on hepatocellular carcinoma surveillance: Biopsy for all, some, or none?
Authors: Massimo Iavarone, Angelo Sangiovanni
Journal: Hepatology (2011)

We read with interest the article by Khalili et al.1 addressing the management of small liver nodules detected in patients with cirrhosis under surveillance with abdominal ultrasound (US) that gave indeterminate results by contrast imaging. To optimize American Association for the Study of the Liver Disease (AASLD) guidelines,2 the authors suggest performing a fine-needle biopsy examination of nodules showing either arterial hypervascularity on computed tomography (CT) / magnetic resonance imaging (MRI) or accompanied by a synchronous hepatocellular carcinoma (HCC) only, since these were the only independent variables associated with malignancy in their retrospective study. According to this algorithm, approximately 20% of additional tumors will be identified, with a sensitivity of 62%, a specificity of 79%, and a 73% save of liver biopsies. When we applied this algorithm to our patients with a de novo liver nodule prospectively detected during surveillance3 (Fig. 1), the corresponding figures were 44% for sensitivity and 55% for specificity, with a positive predictive value of 44% and a negative predictive value of 55%, respectively. Overall, among 36 1-2 cm indeterminate nodules the modified algorithm would have diagnosed 7 (44%) of tumors only of the 16 identified by histology, including 15 HCC and 1 intrahepatic cholangiocarcinoma (ICC). At the same time, the diagnosis of HCC would have been significantly delayed in nine (56%) patients compared with none if treated according to AASLD guidelines. The fact that the majority (75%) of delayed diagnoses were in patients with a very early HCC, i.e., the ideal candidates for radical treatment with local ablation,4 attenuates the appeal of the modified algorithm, which in addition would have also led to a misdiagnosis of ICC in one nodule devoid of contrast uptake during the arterial phase of CT/MRI. Due to the high incidence of HCC in patients with compensated cirrhosis and the low risk of liver biopsy complications, we strongly endorse unmodified AASLD guidelines for the management of patients with cirrhosis with 1-2 cm liver nodules with undefined radiological diagnosis. The diagnostic yield of revised AASLD algorithm in our patients undergoing surveillance. Liver histology was the gold standard for the diagnosis of 1-2 cm HCC. Massimo Iavarone M.D.*, Angelo Sangiovanni M.D.*, * A.M. & A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy.
Immune evasion in cancer: Mechanistic basis and therapeutic strategies
Authors: Dass S. Vinay, Elizabeth P. Ryan, Graham Pawelec, Wamidh H. Talib, John Stagg, Eyad Elkord, Terry Lichtor, William K. Decker, Richard L. Whelan, H.M.C. Shantha Kumara, Emanuela Signori, Kanya Honoki, Alexandros G. Georgakilas, Amr Amin, William G. Helferich, Chandra S. Boosani, Gunjan Guha, Maria Rosa Ciriolo, Sophie Chen, Sulma I. Mohammed, Asfar S. Azmi, W. Nicol Keith, Alan Bilsland, Dipita Bhakta, Dorota Halicka, Hiromasa Fujii, Katia Aquilano, S. Salman Ashraf, Somaira Nowsheen, Xujuan Yang, Beom K. Choi, Byoung S. Kwon
Journal: Seminars in Cancer Biology (2015)

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through “equilibrium” and “senescence” before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.
ROUND ULCER OF THE STOMACH.
Authors: HENRY M. LYMAN
Journal: JAMA (1897)

The patient whom I shall exhibit to you this morning is a young woman, 23 years of age, unmarried, and by occupation a cook. She is of good figure, plump and apparently well nourished. But her countenance is abnormally pallid; the naso-labial lines are deeply chiseled around the corners of her mouth, and there is about her face an expression of painful anxiety that is unnatural in one so young. She tells us that for three years she suffered with uneasy, gnawing sensations behind the tip of the ensiform cartilage, and that these were aggravated by food or drink, or by the accumulation of gas in the stomach. Sometimes she felt a similar pain between the shoulder blades, usually near or under the tip of the right scapula. Still, she was able to work, and made very little complaint until one day, six weeks ago, she experienced a feeling as
Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: soluble pronucleating proteins in gallbladder and hepatic biles
Authors: Karel J. van Erpecum, David Q.-H. Wang, Frank Lammert, Beverly Paigen, Albert K. Groen, Martin C. Carey
Journal: Journal of Hepatology (2001)
The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design
Authors: Nina M. van Sorge, Jason N. Cole, Kirsten Kuipers, Anna Henningham, Ramy K. Aziz, Ana Kasirer-Friede, Leo Lin, Evelien T.M. Berends, Mark R. Davies, Gordon Dougan, Fan Zhang, Samira Dahesh, Laura Shaw, Jennifer Gin, Madeleine Cunningham, Joseph A. Merriman, Julia Hütter, Bernd Lepenies, Suzan H.M. Rooijakkers, Richard Malley, Mark J. Walker, Sanford J. Shattil, Patrick M. Schlievert, Biswa Choudhury, Victor Nizet
Journal: Cell Host & Microbe (2014)
Bradykinin in carcinoid syndrome.
Authors: J Gustafsen, S Boesby, F Nielsen, J Giese
Journal: Gut (1987)

Bradykinin concentrations in peripheral venous blood were measured in seven patients with carcinoid syndrome. The diagnosis was based on typical symptoms and raised urinary excretion of 5-hydroxy-3-indole acetic acid; the carcinoid tumour was verified histologically. Two patients were flushing constantly and the other patients had flushing attacks two to 10 times daily. Several blood samples were taken at weekly intervals from six of seven patients. During 30 sampling procedures the patients were flushing during sampling in 12 instances. Bradykinin was measured by a sensitive solid phase radioimmunoassay technique. Blood bradykinin concentration was normal in all patients. Bradykinin is unlikely to be the vasoactive mediator of flushing.
Interaction of metals during their uptake and accumulation in rabbit renal cortical slices.
Authors: R L Keith, S J McGuinness, A J Gandolfi, T P Lowe, Q Chen, Q Fernando
Journal: Environmental Health Perspectives (1995)

The uptake and accumulation of metals occurs in the kidney, which is a key site for interaction between metal nephrotoxicants. The uptake/accumulation and interaction of CdCl2, HgCl2, K2Cr2O7, and NaAsO2 was examined in precision-cut rabbit renal cortical slices. Slices were incubated with 10(-6) to 10(-3) M of a single metal toxicant or combinations of metal toxicants for 12 hr in DME-F12 media. Slices were blotted and sandwiched between two mylar films stretched across XRF sample cups. Quantitation of the metal in the slices was performed by proton-induced X-ray emission analysis (PIXE). The uptake of the metals was rapid, often reaching a maximum between 3 to 6 hr; the accumulation of Hg was highest, followed in order by Cd, Cr, and As. When two metals were present together, substantial alterations were observed in the uptake of the metals in the slices. HgCl2 hindered the uptake of K2Cr2O7, NaAsO2, CdCl2 (in this order), whereas these metals facilitated the uptake of HgCl2. However, a decreased uptake of both metals was often noted after exposure to other combinations of metals. PIXE analysis of metal content in slices is attractive since all elements (atomic number > 20) can be determined simultaneously. This information will be particularly useful in studying potential toxic interactions.
Food Standards Agency must do more to protect public health
Authors: S. Mayor
Journal: BMJ (2003)

The Food Standards Agency should be more active in initiatives to protect public health and consumers' interests in relation to food, a parliamentary audit of its work said this week.

The audit by the House of Commons Committee of Public Accounts—a group of members of parliament that scrutinises use of public funds—recommended that the agency should take a stronger stance as “the champion of the consumer.”

The …
Chronic Fructose Intoxication after Infancy in Children with Hereditary Fructose Intolerance
Authors: Donald M. Mock, Jay A. Perman, M. Michael Thaler, R. Curtis Morris
Journal: New England Journal of Medicine (1983)

In two unrelated boys, 5.3 and 3.8 years of age, with hereditary fructose intolerance, apparently isolated growth retardation (-2.71 S.D. and -2.40 S.D.) occurred after infancy, even though acute symptomatic fructose intoxication was prevented by restriction of dietary fructose. When more stringent restriction of dietary fructose was instituted (approximately 40 mg per kilogram of body weight per day), growth velocity increased from the 25th to the 97th percentile in one child and from well below the 3d to above the 75th percentile in the other. When restriction of dietary fructose was experimentally relaxed (from 10 to 250 mg per kilogram per day), neither boy had symptoms, hypoglycemia, or evidence of hepatic or renal dysfunction, but both had sustained hyperuricemia and hyperuricosuria and increases in the plasma concentration and urinary excretion of magnesium. We conclude that in patients with hereditary fructose intolerance, clinically important chronic fructose intoxication can occur after infancy without causing symptoms of acute fructose intoxication and can be expressed as an apparently isolated, reversible retardation of somatic growth with a continuing disorder of adenine nucleotide metabolism, characterized in part by recurrently increased rates of degradation of adenine nucleotides. (N Engl J Med 1983; 309:764–70.)
Health-Related Quality of Life and Metabolic Control in Children With Type 1 Diabetes
Authors: Kylie D. Hesketh, Melissa A. Wake, Fergus J. Cameron
Journal: Diabetes Care (2004)

OBJECTIVE—To assess change in health-related quality of life (HRQOL) in children with diabetes over 2 years and determine its relationship to change in metabolic control. RESEARCH DESIGN AND METHODS—In 1998, parents of children aged 5–18 years attending a tertiary diabetes clinic reported their child’s HRQOL using the Child Health Questionnaire PF-50. Those aged 12–18 years also self-reported their HRQOL using the analogous Child Health Questionnaire CF-80. HbA1c levels were recorded. In 2000, identical measures were collected for those who were aged ≤18 years and still attending the clinic. RESULTS—Of 117 eligible subjects, 83 (71%) participated. Parents reported no significant difference in children’s HRQOL at baseline and follow-up. However, adolescents reported significant improvements on the Family Activities (P &amp;lt; 0.001), Bodily Pain (P = 0.04), and General Health Perceptions (P = 0.001) scales and worsening on the Behavior (P = 0.04) scale. HbA1c at baseline and follow-up were strongly correlated (r = 0.57). HbA1c increased significantly (mean 7.8% in 1998 vs. 8.5% in 2000; P &amp;lt; 0.001), with lower baseline HbA1c strongly predicting an increase in HbA1c over the 2 years (r2 = 0.25, P &amp;lt; 0.001). Lower parent-reported Physical Summary and adolescent-reported Physical Functioning scores at baseline also predicted increasing HbA1c. Poorer parent-reported Psychosocial Summary scores were related to higher HbA1c at both times but did not predict change in HbA1c. CONCLUSIONS—Changes in parent and adolescent reports of HRQOL differ. Better physical functioning may protect against deteriorating HbA1c, at least in the medium term. While the HRQOL of children with diabetes does not appear to deteriorate over time, we should not be complacent, as it is consistently poorer than that of their healthy peers.
Gall bladder and bowel: the links multiply
Authors: K W HEATON
Journal: Gut (1999)

<h3>Abstract</h3> Epstein-Barr Virus (EBV) infection of B lymphocytes elicits diverse host responses via complex, well-adapted transcriptional control dynamics. Consequently, this host-pathogen interaction provides a powerful system to explore fundamental cellular processes that contribute to consensus fate decisions including cell cycle arrest, apoptosis, proliferation, and differentiation. Here we capture these responses and fates with matched single-cell transcriptomics and chromatin accessibility, from which we construct a genome-wide multistate model of early infection dynamics. Notably, our model captures a previously uncharacterized EBV<sup>+</sup> analog of a multipotent activated precursor state that can yield early memory B cells. We also find that a marked global reduction in host chromatin accessibility occurs during the first stages of infection in subpopulations of EBV<sup>+</sup> cells that display senescent and pre-apoptotic hallmarks induced by innate antiviral sensing and proliferation-linked DNA damage. However, cells in proliferative infection trajectories exhibit greater accessibility at select host sites linked to B cell activation and survival genes as well as key regions within the viral genome. To further investigate such loci, we implement a bioinformatic workflow (crisp-ATAC) to identify phenotype-resolved regulatory signatures. This customizable method applies user-specified logical criteria to produce genome-wide single-cell ATAC- and ChIP-seq range intersections that are used as inputs for <i>cis</i>-linkage prediction and ontology tools. The resulting tri-modal data yield exquisitely detailed hierarchical perspectives of the transforming regulatory landscape during critical stages of an oncogenic viral infection that simulates antigen-induced B cell activation and differentiation. We anticipate these resources will guide investigations of gene regulatory modules controlling EBV-host dynamics, B cell effector fates, and lymphomagenesis.
Judge rules not to resuscitate baby despite some improvement
Authors: Clare Dyerlegal
Journal: BMJ (2005)

BMJ Clare Dyer legal correspondent 

The parents of Charlotte Wyatt, a 15 month old brain damaged baby at the centre of a battle over treatment to prolong her life, failed last week in their attempt to persuade a High Court judge to lift his earlier order authorising doctors not to ventilate her if her condition worsens.

Darren and Debbie Wyatt had asked Mr Justice Hedley to suspend the order pending a hearing before Easter in which they hope to persuade him to lift it altogether on the grounds that her condition has …
Local Similarity in Evolutionary Rates Extends over Whole Chromosomes in Human-Rodent and Mouse-Rat Comparisons: Implications for Understanding the Mechanistic Basis of the Male Mutation Bias
Authors: Martin J. Lercher, Elizabeth J. B. Williams, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2001)

The sex chromosomes and autosomes spend different times in the germ line of the two sexes. If cell division is mutagenic and if the sexes differ in number of cell divisions, then we expect that sequences on the X and Y chromosomes and autosomes should mutate at different rates. Tests of this hypothesis for several mammalian species have led to conflicting results. At the same time, recent evidence suggests that the chromosomal location of genes on autosomes affects their rate of evolution at synonymous sites. This suggests a mutagenic source different from germ cell replication. To correctly interpret the previous estimates of male mutation bias, it is crucial to understand the degree and range of this local similarity. With a carefully chosen randomization protocol, local similarity in synonymous rates of evolution can be detected in human-rodent and mouse-rat comparisons. However, the synonymous-site similarity in the mouse-rat comparison remains weak. Simulations suggest that this difference between the mouse-human and the mouse-rat comparisons is not artifactual and that there is therefore a difference between humans and rodents in the local patterns of mutation or selection on synonymous sites (conversely, we show that the previously reported absence of a local similarity in nonsynonymous rates of evolution in the human-rodent comparison was a methodological artifact). We show that linkage effects have a long-range component: not one in a million random genomes shows such levels of autosomal heterogeneity. The heterogeneity is so great that more autosomes than expected by chance have rates of synonymous evolution comparable with that of the X chromosome. As autosomal heterogeneity cannot be owing to different times spent in the germ line, this demonstrates that the dominant determiner of synonymous rates of evolution is not, as has been conjectured, the time spent in the male germ line.
From electronic gadgets to better health: where is the knowledge?
Authors: A. R Jadad
Journal: BMJ (2003)

A call for papers for the BMJ theme issue on eHealth applications 

Over the past decade, we have been exposed to an unprecedented number of information and communication technologies that have promised to affect health care. We have witnessed the breathtaking expansion of the internet and the launch of numerous personal electronic assistants, with smart phones and wireless personal organisers leading the pack. Most high income countries have allocated substantial resources to integrating electronic health information systems and many of their citizens now have access to the internet.

During the same decade some disturbing changes took place. Most “dot com” companies rose and fell, leaving their promises for radical change unfulfilled. In the countries with the requisite tools and the infrastructure, doctors continued …
Fibrin microbeads (FMB) as a 3D platform for kidney gene and cell therapy
Authors: N. Shimony, R. Gorodetsky, G. Marx, D. Gal, R. Rivkin, A. Ben-Ari, A. Landsman, Y.S. Haviv
Journal: Kidney International (2006)

Cell and gene therapy may alter the outcome of renal diseases, such as hereditary nephropathies, acute and chronic glomerulonephritis and allograft nephropathy. However, owing to blockade of many viral and cellular vehicles by the complex glomerular architecture, the exact nature of gene and cell delivery into specific renal compartments remains currently unknown. To study the interaction of viral vectors with a variety of renal cells and mesenchymal stem cells (MSCs), we employed a novel biological three-dimensional (3D) matrix comprised of fibrin microbeads (FMB) in comparison to monolayer cell culture. Our studies showed that renal cells of both established and primary lines can grow efficiently on FMB and differentiate into epithelial structures, as shown by electron microscopy. Gene delivery into renal cells in 3D was observed for several viral vectors and growth in 3D on FMB conferred resistance to renal cancer cells in the context of oncolytic adenoviruses. Finally, MSCs from various rodent species attached to FMB, grew robustly, survived for several weeks and could efficiently be transduced on FMB. Thus, on the basis of growth, differentiation and transduction of renal cells in 3D, FMB emerge as a novel 3D cellular microenvironment that differs substantially from monolayer cell cultures.
Metabolism of cerebroside sulfate and subcellular distribution of its metabolites in cultured skin fibroblasts from controls, metachromatic leukodystrophy, and globoid cell leukodystrophy.
Authors: K Inui, M Furukawa, S Okada, H Yabuuchi
Journal: Journal of Clinical Investigation (1988)

With pulse-chase study of 1-[14C]stearic acid-labeled cerebroside sulfate (14C-CS) and subsequent subcellular fractionation by Percoll gradient, the metabolism of CS and translocation of its metabolites in human skin fibroblasts from controls, metachromatic leukodystrophy (MLD), and globoid cell leukodystrophy (GLD) were studied. In control skin fibroblasts, CS was transported to lysosome and metabolized there to galactosylceramide (GalCer) and ceramide (Cer) within 1 h. During the chase period, radioactivity was increased at plasma membrane plus Golgi as phospholipids and no accumulation of GalCer or Cer was found in lysosome. In MLD fibroblasts, 95% of 14C-CS taken up was unhydrolyzed at 24 h-chase and accumulated at not only lysosome but also plasma membrane. In GLD fibroblasts, GalCer was accumulated throughout the subcellular fractions and more accumulated mainly at plasma membrane plus Golgi with longer pulse. This translocation of lipid from lysosome seems to have considerable function, even in lipidosis, which may result in an imbalance of the sphingolipid pattern on the cell surface and these changes might be one of causes of neuronal dysfunction in sphingolipidosis.
Diabetes mellitus and prostatic hyperplasia.
Authors: B. Lake
Journal: BMJ (1968)

limiting screening to women over 35 years, but as there has not been an overwhelming demand for the interpretation of smears these days are past.Incidentally in our area, where the incidence of cervical cancer is falling,' there have been no fewer than five women with overt clinical cervical cancer in the past two years who were multiparous and under 30 years of age.-I am, etc.,
Elevated serum aminotransferase induced by isoniazid in relation to isoniazid acetylator phenotype
Authors: Tetsuo Yamamoto, Takeaki Suou, Chisato Hirayama
Journal: Hepatology (1986)

Of 143 patients with pulmonary tuberculosis receiving isoniazid therapy, 52 (36%) had a transient elevation in serum aminotransferases. Among 74 patients taking isoniazid, rifampicin and streptomycin, 35 (47%) had such an increase, while of 69 patients taking isoniazid, amino–salicylic acid and streptomycin, 17 (24%) did; this difference was significant. Isoniazid therapy could be continued in all patients with the abnormal test results. In 36 of the patients receiving isoniazid, rifampicin and streptomycin, isoniazid and its metabolites were studied in the serum and urine using high–performance liquid chromatography after the oral administration of 10 mg per kg of isoniazid. We had chosen for this test 18 patients with normal aminotransferase levels and 18 with abnormal levels. There were 14 rapid acetylators in the patients with abnormal aminotransferase levels and 7 rapid acetylators in the patients with normal levels; this difference was significant. These results indicate that liver dysfunction is more often caused by an isoniazid/rifampicin regimen, and patients who are rapid acetylators are more susceptible.