tbuckley/cabot-search huggingface dataset:
Proximal myopathy and bone pain as the presenting features of coeliac disease
Authors: M Wong
Journal: Annals of the Rheumatic Diseases (2002)

It is rare for coeliac disease to present only with symptoms of osteomalacia, without the classic symptoms of diarrhoea, steatorrhoea, and abdominal discomfort.1–5

A 22 year old woman presented with 18 months of a waddling gait disturbance. Hip and back x rays were normal. She experienced bone pain when being hugged, when laughing, or coughing, and had difficulty standing up from a low chair and holding her arms up to blow-dry her hair. She had extreme tiredness and thought she might have lost some weight, but there were no gastrointestinal symptoms.

On examination, she was pale and had difficulty squatting and holding her arms above her head.

Investigations showed a mild anaemia secondary to β thalassaemia minor and iron deficiency. Other investigations disclosed a raised alkaline phosphatase of 1375 U/l (normal 30–120 U/l), reduced red blood cell folate level of 290 nmol/l (>300 nmol/l), corrected calcium of 1.75 mmol/l (2.15–2.65 mmol/l), phosphate 1.0 mmol/l (0.8–1.4 mmol/l), 25-hydroxy vitamin D <5 nmol/l …
Cardiac Responses to Transthoracic Capacitor Discharges in the Dog
Authors: WILLIAM R. MILNOR, G. GUY KNICKERBOCKER, WILLIAM B. KOUWENHOVEN
Journal: Circulation Research (1958)

Many previous investigators have presented data suggesting that the processes involved in excitation and recovery in heart muscle limit the "vulnerable period" to a relatively small part of the heart cycle in late systole. Evidence presented in this report indicates that there are exceptions to this rule, at least in the intact animal, since under some conditions multiple extrasystoles and ventricular fibrillation can be elicited by single stimuli of short duration and high voltage applied at almost any time in systole or diastole.
‘Blind’ antibiotic treatment targeting Chlamydia is not effective in patients with MALT lymphoma of the ocular adnexa
Authors: B. Grünberger, W. Hauff, J. Lukas, S. Wöhrer, C.C. Zielinski, B. Streubel, A. Chott, M. Raderer
Journal: Annals of Oncology (2006)
Sudden Death and Use of Stimulant Medications in Youths
Authors: Madelyn S Gould, B Timothy Walsh, Jimmie Lou Munfakh, Marjorie Kleinman, Naihua Duan, Mark Olfson, Laurence Greenhill, Thomas Cooper
Journal: American Journal of Psychiatry (2009)

The authors sought to determine whether a significant association exists between the use of stimulants and the rare event of sudden unexplained death in children and adolescents.A matched case-control design was performed. Mortality data from 1985-1996 state vital statistics were used to identify 564 cases of sudden death occurring at ages 7 through 19 years across the United States along with a matched group of 564 young people who died as passengers in motor vehicle traffic accidents. The primary exposure measure was the presence of amphetamine, dextroamphetamine, methamphetamine, or methylphenidate according to informant reports or as noted in medical examiner records, toxicology results, or death certificates.In 10 (1.8%) of the sudden unexplained deaths it was determined that the youths were taking stimulants, specifically methylphenidate; in contrast, use of stimulants was found in only two subjects in the motor vehicle accident comparison group (0.4%), with only one involving methylphenidate use. A significant association of stimulant use with sudden unexplained death emerged from the primary analysis, which was based on exact conditional logistic regression (odds ratio=7.4, 95% CI=1.4 to 74.9). A comprehensive series of sensitivity analyses yielded qualitatively similar findings.This case-control study provides support for an association between the use of stimulants and sudden unexplained death among children and adolescents. Although sudden unexplained death is a rare event, this finding should be considered in the context of other data about the risk and benefit of stimulants in medical treatment.
Virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) in patients with type B hepatitis
Authors: Atsushi Kanno, Hitoshi Ohori, Keizaburoh Matsuda, Haruo Nakayama, Yutaka Miyazaki, Motoyasu Ishii, Hiroshi Suzuki, Masao Ohtsuki, Yoshio Goto
Journal: Hepatology (1987)

In order to establish the virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) during hepatitis B virus infection, HBsAg, HBeAg and hepatitis B virus DNA in serum and HBeAg in liver were determined quantitatively in relation to the detection of HBeAg subtypes in agar gel diffusion. Thirty-eight chronic HBsAg carriers with HBeAg, including 16 non-specific reactive hepatitis, 8 chronic persistent hepatitis, 11 chronic active hepatitis and 3 liver cirrhosis, who were seen at Tohoku University Hospital from 1983 to 1985, were examined. Significantly larger amounts of HBsAg, HBeAg and hepatitis B virus DNA in serum and HBeAg in liver were found in patients positive for both HBeAg/1 and HBeAg/2 in serum than in those positive for only HBeAg/1 or negative for both subtypes. These results suggest that the presence of HBeAg/2 in serum may reflect the occurrence of active viral replication. When the detection pattern of HBeAg subtypes was examined during serial follow-up for at least 1 year, three groups of patients were classified with respect to the presence of HBeAg/2, i.e., Type I, consistently positive for HBeAg/2, Type II, consistently negative for HBeAg/2, and Type III, intermittently positive for HBeAg/2. More than 80% of Type I patients were histologically diagnosed having as nonspecific reactive hepatitis, while more than 80% of Type II and III patients had more progressive liver diseases such as chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis. These results suggest that the serial examination of HBeAg subtypes in serum may be important for more detailed evaluations of type B hepatitis.
Roles of cis- and trans-Changes in the Regulatory Evolution of Genes in the Gluconeogenic Pathway in Yeast
Authors: Y.-W. Chang, F.-G. Robert Liu, N. Yu, H.-M. Sung, P. Yang, D. Wang, C.-J. Huang, M.-C. Shih, W.-H. Li
Journal: Molecular Biology and Evolution (2008)

The yeast Saccharomyces cerevisiae proliferates rapidly in glucose-containing media. As glucose is getting depleted, yeast cells enter the transition from fermentative to nonfermentative metabolism, known as the diauxic shift, which is associated with major changes in gene expression. To understand the expression evolution of genes involved in the diauxic shift and in nonfermentative metabolism within species, a laboratory strain (BY), a wild strain (RM), and a clinical isolate (YJM) were used in this study. Our data showed that the RM strain enters into the diauxic shift ∼1 h earlier than the BY strain with an earlier, higher induction of many key transcription factors (TFs) involved in the diauxic shift. Our sequence data revealed sequence variations between BY and RM in both coding and promoter regions of the majority of these TFs. The key TF Cat8p, a zinc-finger cluster protein, is required for the expression of many genes in gluconeogenesis under nonfermentative growth, and its derepression is mediated by deactivation of Mig1p. Our kinetic study of CAT8 expression revealed that CAT8 induction corresponded to the timing of glucose depletion in both BY and RM and CAT8 was induced up to 50- to 90-folds in RM, whereas only 20- to 30-folds in BY. In order to decipher the relative importance of cis- and trans-variations in expression divergence in the gluconeogenic pathway during the diauxic shift, we studied the expression levels of MIG1, CAT8, and their downstream target genes in the cocultures and in the hybrid diploids of BY–RM, BY–YJM, and RM–YJM and in strains with swapped promoters. Our data showed that the differences between BY and RM in the expression of MIG1, the upstream regulator of CAT8, were affected mainly by changes in cis-elements, though also by changes in trans-acting factors, whereas those of CAT8 and its downstream target genes were predominantly affected by changes in trans-acting factors.
Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis
Authors: Ian J. Griswold, Lei J. Shen, Paul La Rosée, Shadmehr Demehri, Michael C. Heinrich, Rita M. Braziel, Laura McGreevey, Andrea D. Haley, Neill Giese, Brian J. Druker, Michael W.N. Deininger
Journal: Blood (2004)
Functional upper airway obstruction and chronic irritation of the larynx
Authors: TB Rothe, W Karrer
Journal: European Respiratory Journal (1998)

Wheezing and dyspnoea are typical symptoms of asthma but can also be found in diseases of the extrathoracic airways. Functional upper airway obstruction may imitate, as well as complicate asthma. Functional upper airway obstruction was first described as a conversion disorder in young females with inspiratory stridor. Subsequently, it was found that functional upper airway obstruction was more often a secondary phenomenon in chronic asthma also involving the expiratory laryngeal airflow. During a period of 15 months, we diagnosed six cases of functional upper airway obstruction. Five patients were female and one male, and four were also asthmatics. Three cases showed chronic sinusitis with postnasal drip (PND) and/or gastro-oesophageal reflux. Both disorders may irritate the larynx. Treatment of sinusitis and gastro-oesophageal reflux led to a significant improvement of dyspnoea in all three of these patients. In asthma refractory to treatment and in the case of an asthmatic exacerbation without obvious cause, functional upper airway obstruction should be excluded to avoid unnecessary treatment with systemic steroids. Some of the possible causative factors of functional upper airway obstruction, such as postnasal drip and gastro-oesophageal reflux, are easily treatable.
From the authors
Authors: C. Jafari, M. Ernst, C. Lange
Journal: European Respiratory Journal (2008)

as the stimulatory antigen [5,6].This is probably due to lymphocytes that are primed in dendritic cells in the skin recirculating to local lymph nodes and the spleen, but not the lung.Therefore, we suggest that flow cytometry provides more relevant information regarding lung lymphocyte responses and that purified protein derivative has several advantages over RD-1 antigens in this context.
Prevention of diabetic nephropathy in db/db mice with glycated albumin antagonists. A novel treatment strategy.
Authors: M P Cohen, K Sharma, Y Jin, E Hud, V Y Wu, J Tomaszewski, F N Ziyadeh
Journal: Journal of Clinical Investigation (1995)

Accelerated protein glycation in diabetes has been mechanistically linked to the pathogenesis of diabetic nephropathy. Because glycated albumin induces abnormalities in cultured mesangial cells that resemble those characterizing the glomerular mesangium in diabetes, and monoclonal antibodies (A717) specific for Amadori-modified glycated albumin prevent these abnormalities, we postulated that in vivo administration of A717 could retard the progression of diabetic nephropathy. To test this hypothesis, diabetic db/db mice and their nondiabetic db/m littermates were treated with eight consecutive weekly injections of 150 micrograms of A717 (Fab fragments) to reduce the elevated plasma glycated albumin concentration, or with irrelevant murine IgG (MIg). Relative to nondiabetics, diabetic mice (MIg treated) manifested proteinuria (3.35 +/- 0.15 vs 0.87 +/- 0.1 mg albumin/mg creatinine), 3.8-fold increase in mesangial matrix fraction, and renal cortical overexpression of mRNAs encoding alpha 1(IV) collagen (2.6-fold increase) and fibronectin (3.8-fold increase). Treatment of db/db mice with A717 significantly reduced the proteinuria (1.52 +/- 0.3 mg/mg creatinine), inhibited mesangial matrix expansion, and attenuated overexpression of matrix mRNAs. The nephropathic protective effects of A717 were independent of any change in blood glucose concentrations. Antibodies unreactive with glycated albumin did not duplicate the beneficial effects of A717. Thus, abrogating the biologic effects of increased glycated albumin with A717 has a salutary influence on the pathogenesis of diabetic nephropathy and has novel therapeutic potential in its management.
Functional Parsing of Driver Mutations in the Colorectal Cancer Genome Reveals Numerous Suppressors of Anchorage-Independent Growth
Authors: Ugur Eskiocak, Sang Bum Kim, Peter Ly, Andres I. Roig, Sebastian Biglione, Kakajan Komurov, Crystal Cornelius, Woodring E. Wright, Michael A. White, Jerry W. Shay
Journal: Cancer Research (2011)

Landmark cancer genome resequencing efforts are leading to the identification of mutated genes in many types of cancer. The extreme diversity of mutations being detected presents significant challenges to subdivide causal from coincidental mutations to elucidate how disrupted regulatory networks drive cancer processes. Given that a common early perturbation in solid tumor initiation is bypass of matrix-dependent proliferation restraints, we sought to functionally interrogate colorectal cancer candidate genes (CAN-genes) to identify driver tumor suppressors. We have employed an isogenic human colonic epithelial cell (HCEC) model to identify suppressors of anchorage-independent growth by conducting a soft agar-based short hairpin RNA (shRNA) screen within the cohort of CAN-genes. Remarkably, depletion of 65 of the 151 CAN-genes tested collaborated with ectopic expression of K-RAS(V12) and/or TP53 knockdown to promote anchorage-independent proliferation of HCECs. In contrast, only 5 of 362 random shRNAs (1.4%) enhanced soft agar growth. We have identified additional members of an extensive gene network specifying matrix-dependent proliferation, by constructing an interaction map of these confirmed progression suppressors with approximately 700 mutated genes that were excluded from CAN-genes, and experimentally verifying soft agar growth enhancement in response to depletion of a subset of these genes. Collectively, this study revealed a profound diversity of nodes within a fundamental tumor suppressor network that are susceptible to perturbation leading to enhanced cell-autonomous anchorage-independent proliferative fitness. Tumor suppressor network fragility as a paradigm within this and other regulatory systems perturbed in cancer could, in large part, account for the heterogeneity of somatic mutations detected in tumors.
Destructive large joint arthritis.
Authors: M Regan, J K Lloyd Jones, J Snape
Journal: Annals of the Rheumatic Diseases (1995)

<h3>Background</h3> To evaluate regional disparities in the influence of diabetes on population health, we examine life expectancies at age 50 between population with diabetes and healthy population and life quality among the population with diabetes among native-born Americans by birth region and current residence. <h3>Methods</h3> Using data on a cohort of 17 686 native-born individuals from the Health and Retirement Survey (1998–2014), we applied a Bayesian multistate life table method to estimate life expectancies at age 50 between population with diabetes and healthy population by each birth/current region combination. We further estimate the proportion of life remaining without either chronic conditions or disabilities as a quality of life measure and the probabilities that one region is worse than the other in terms of different health outcomes. <h3>Results</h3> At age 50, persons with diabetes (PWD) were expected to live on average 5.8–10.8&nbsp;years less than their healthy equivalents across regions. Diabetes had the greatest influence on life expectancy (LE) for older adults who lived in the South at the time of interviews. PWD born in the South were more likely to have developed chronic conditions or disabilities and spent greater proportions of life with these two issues compared to other regions. <h3>Conclusion</h3> Diabetes is a significant threat to LE and healthy LE in the USA, particularly for people born or living in the South.
Regulation of Cell Survival and Death by Pyridine Nucleotides
Authors: Shin-ichi Oka, Chiao-Po Hsu, Junichi Sadoshima
Journal: Circulation Research (2012)

Pyridine nucleotides (PNs), such as NAD(H) and NADP(H), mediate electron transfer in many catabolic and anabolic processes. In general, NAD + and NADP + receive electrons to become NADH and NADPH by coupling with catabolic processes. These electrons are utilized for biologically essential reactions such as ATP production, anabolism and cellular oxidation-reduction (redox) regulation. Thus, in addition to ATP, NADH and NADPH could be defined as high-energy intermediates and “molecular units of currency” in energy transfer. We discuss the significance of PNs as energy/electron transporters and signal transducers, in regulating cell death and/or survival processes. In the first part of this review, we describe the role of NADH and NADPH as electron donors for NADPH oxidases (Noxs), glutathione (GSH), and thioredoxin (Trx) systems in cellular redox regulation. Noxs produce superoxide/hydrogen peroxide yielding oxidative environment, whereas GSH and Trx systems protect against oxidative stress. We then describe the role of NAD + and NADH as signal transducers through NAD + -dependent enzymes such as PARP-1 and Sirt1. PARP-1 is activated by damaged DNA in order to repair the DNA, which attenuates energy production through NAD + consumption; Sirt1 is activated by an increased NAD + /NADH ratio to facilitate signal transduction for metabolic adaption as well as stress responses. We conclude that PNs serve as an important interface for distinct cellular responses, including stress response, energy metabolism, and cell survival/death.
Resveratrol impairs the release of steroid-resistant cytokines from bacterial endotoxin-exposed alveolar macrophages (AM) in COPD
Authors: Jurgen Knobloch, David Jungck, Katja Urban, Andrea Koch
Journal: European Respiratory Journal (2011)

Airway inflammation in COPD might be insensitive to corticosteroids. However, corticosteroids are recommended in COPD (GOLD stages III, IV) with frequent exacerbations. Resveratrol has anti-inflammatory properties and could be an alternative in COPD therapy.  We investigated the effect of dexamethasone (Dex) versus resveratrol on the release of COPD-related inflammatory mediators (IL-6, IL-8, GM-CSF, MCP1) and MMP9 from AM exposed to bacterial endotoxin (lipopolysaccharide, LPS). We compared never-smokers (NS), current smokers without airway obstruction (S) and current smokers with COPD (each n=12). Cytokines and MMP9 were measured in cell culture supernatants with ELISA.  The release of IL-8 and MMP9 from LPS-exposed AM was increased in COPD (each p  Our data provide evidence for a corticosteroid-resistance of AM-dependent inflammatory responses induced by gram-negative bacteria in COPD and thus question the utility of corticosteroids in COPD therapy. Instead, resveratrol may prove an alternative.
On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells
Authors: Inbal Avraham-Davidi, Simon Yona, Myriam Grunewald, Limor Landsman, Clement Cochain, Jean Sebastien Silvestre, Haim Mizrahi, Mohammad Faroja, Dalit Strauss-Ayali, Matthias Mack, Steffen Jung, Eli Keshet
Journal: The Journal of Experimental Medicine (2013)

Adult neovascularization relies on the recruitment of monocytes to the target organ or tumor and functioning therein as a paracrine accessory. The exact origins of the recruited monocytes and the mechanisms underlying their plasticity remain unclear. Using a VEGF-based transgenic system in which genetically tagged monocytes are conditionally summoned to the liver as part of a VEGF-initiated angiogenic program, we show that these recruited cells are derived from the abundant pool of circulating Ly6Chi monocytes. Remarkably, however, upon arrival at the VEGF-induced organ, but not the naive organ, monocytes undergo multiple phenotypic and functional changes, endowing them with enhanced proangiogenic capabilities and, importantly, with a markedly increased capacity to remodel existing small vessels into larger conduits. Notably, monocytes do not differentiate into long-lived macrophages, but rather appear as transient accessory cells. Results from transfers of presorted subpopulations and a novel tandem transfer strategy ruled out selective recruitment of a dedicated preexisting subpopulation or onsite selection, thereby reinforcing active reprogramming as the underlying mechanism for improved performance. Collectively, this study uncovered a novel function of VEGF, namely, on-site education of recruited “standard” monocytes to become angiogenic and arteriogenic professional cells, a finding that may also lend itself for a better design of angiogenic therapies.
Increased oxidation of extracellular glutathione by bronchoalveolar inflammatory cells in diffuse fibrosing alveolitis
Authors: J Behr, B Degenkolb, K Maier, B Braun, T Beinert, F Krombach, C Vogelmeier, G Fruhmann
Journal: European Respiratory Journal (1995)

An unbalanced oxidative stress is thought to be an important element in the pathogenesis of diffuse fibrosing alveolitis (DFA). The purpose of our study was to investigate the role of reactive oxygen metabolites (ROMs) released from cultured bronchoalveolar inflammatory cells (BA-cells) on glutathione oxidation. We studied bronchoalveolar lavage samples from 10 healthy controls and from 20 patients with diffuse fibrosing alveolitis (all were nonsmokers). BA-cells obtained by bronchoalveolar lavage (BAL) were incubated with 50 microM of reduced glutathione (GSH). Oxidation of GSH to glutathione disulphide (GSSG) by BA-cell derived oxidants was detected as a decline of GSH in the supernatants. Total glutathione (GSHtot = GSH + 2 GSSG) and GSSG in the epithelial lining fluid (ELF), and methionine sulphoxide (Met(O)) content of BAL proteins were determined. In diffuse fibrosing alveolitis the oxidative activity of BA-cells was enhanced, GSHtot and GSH were decreased, whereas the GSSG:GSH ratio was increased. The oxidative activity of BA-cells correlated positively with the GSSG:GSH ratio, but not with the methionine sulphoxide content. The methionine sulphoxide content was elevated in diffuse fibrosing alveolitis and inversely correlated with GSHtot. The methionine sulphoxide content also correlated positively with the percentage of BAL neutrophils. We conclude that BA-cell-derived reactive oxygen species are capable of oxidizing extracellular GSH in vitro. The positive correlation between the BA-cell oxidative activity in vitro and GSSG:GSH ratio in ELF suggests that a similar oxidative effect on extracellular GSH may also occur in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Junior surgeons are becoming deskilled as result of Calman proposals
Authors: F D. Skidmore
Journal: BMJ (1997)

Editor—With internal cover, I and three colleagues maintain a 1 in 4 surgical rota. Consultants with school aged children take holidays at Christmas, at Easter, and in August. The more senior consultants and those without children bear the brunt of increased on call work during these periods.

During March this year I was the duty consultant for 13 nights out of 31. This included a 72 hour midweek shift, a 72 hour weekend shift, and three 48 hour shifts. Hence I …