tbuckley/cabot-search huggingface dataset:
Pathologist cleared over failure to spot signs of abuse
Authors: O. Dyer
Journal: BMJ (2004)

A government pathologist has been cleared by the General Medical Council of serious professional misconduct over his failure to spot signs of abuse in the postmortem examination of a 14 month old boy ( BMJ 2003;327:640).

Just two weeks after Dr Michael Curtis, assistant state pathologist for Northern Ireland, missed spotting multiple rib fractures in David Filipache, the infant's twin brother was admitted to hospital with a fractured skull.

The two baby boys were 11 months old when they were legally adopted in Romania by Geoffrey Briggs, a former missionary, and his wife …
Pulmonary artery pressure variation in patients with connective tissue disease: 24 hour ambulatory pulmonary artery pressure monitoring
Authors: D A Raeside, G Chalmers, J Clelland, R Madhok, A J Peacock
Journal: Thorax (1998)

<h3>BACKGROUND</h3> The specific contribution of secondary pulmonary hypertension to the morbidity and mortality of patients with underlying lung disease can be difficult to assess from single measurements of pulmonary artery pressure. We have studied patients with secondary pulmonary hypertension using an ambulatory system for measuring continuous pulmonary artery pressure (PAP). We chose to study patients with connective tissue disease because they represent a group at high risk of pulmonary vascular disease, but with little disturbance of lung function. <h3>METHODS</h3> Six patients (five with progressive systemic sclerosis and one with systemic lupus erythematosis) were studied. They underwent preliminary cardiopulmonary investigations followed by Doppler echocardiography, right heart catheterisation, and ambulatory pulmonary artery pressure monitoring to measure changes in pressure over a 24 hour period including during a formal exercise test. <h3>RESULTS</h3> All patients had pulmonary hypertension as measured by Doppler echocardiography with estimated pulmonary artery systolic pressures of 40–100 mm Hg. Pulmonary function testing revealed virtually normal spirometric values (mean FEV<sub>1</sub> 86.9% predicted) but marked reduction in CO gas transfer factor (Kco 57.8% predicted). Exercise responses were impaired with mean Vo<sub>2</sub>max 50.6% predicted. Ambulatory PAP monitoring indicated significant changes in pressures with variation in posture and activity throughout 24 hours. Resting PAP did not predict the change in PAP seen on exercise. <h3>CONCLUSION</h3> Conventional methods of assessment of the pulmonary circulation based on single measurements in the supine position may underestimate the stresses faced by the right side of the circulation. This ambulatory system allows monitoring of pulmonary haemodynamics continuously over 24 hours during normal activities of daily living. These measurements may increase our understanding of the contribution made by secondary pulmonary hypertension to the morbidity and mortality of the underlying lung disease.
THE COMPLEMENT BINDING TEST IN RABIES
Authors: Jane L. Berry
Journal: The Journal of Experimental Medicine (1910)

The work of A. Wasserman and his collaborators in the application of the complement binding test of Bordet and Gengou to the diagnosis of syphilis and other diseases has been followed, as is well known, by a long series of investigations, and many observers have confirmed the views of Wasserman.Positive reactions are said to have been found in typhoid, tuberculosis, meningitis and many other diseased conditions.The most striking results have been obtained in the study of syphilis.Many views have been expressed with regard to the nature of the reaction.The original claim that specific antigens as well as antibodies could be demonstrated in this manner was soon abandoned, since it was found that the test was obtained not only with specific, but also with normal extracts.The fact that alcoholic extracts were found to be effective showed the active substance to be alcohol soluble or lipoid in nature.Porges and Meier, working under Wasserman's direction, found that pure lecithin was able to bind complement with syphilitic sera, and it was evident later that a large number of other lipoids acted as well or even better than lecithin.Meantime Landsteiner and Stankovie had obtained similar results with numerous organically suspended and colloid dissolved substances: Axamit, working with bacterial extracts, had found that these alone bind complement, while Uhlenhuth had found binding with a long list of the most unrelated and diverse materials.None of these results have been held to affect the value of the test in the opinion of its supporters, since it is their claim that complement binding can be obtained 0nly by the action of specific, never of normal sera, or, if the contrary is ever true, it is said to be
Oligomerization Domain of the Multidrug Resistance–Associated Transporter ABCG2 and Its Dominant Inhibitory Activity
Authors: Junkang Xu, Hui Peng, Qun Chen, Yang Liu, Zizheng Dong, Jian-Ting Zhang
Journal: Cancer Research (2007)

Abstract Overexpression of human ATP-binding cassette transporter ABCG2 in cancer cells causes multidrug resistance by effluxing anticancer drugs. ABCG2 is considered as a half transporter and is thought to function as a homodimer. However, recent evidence suggests that it may exist as a higher form of oligomer consisting of 12 subunits. In this study, we mapped the oligomerization domain of human ABCG2 to its transmembrane domain consisting of TM5-loop-TM6. This oligomerization domain, when expressed alone in HEK293 cells, also forms a homododecamer. Furthermore, this domain has activity that inhibits drug efflux and resistance function of the full-length ABCG2 likely by disrupting the formation of the homo-oligomeric full-length ABCG2. These findings suggest that human ABCG2 may exist and work as a homo-oligomer by interactions located in TM5-loop-TM6, and that ABCG2 oligomerization may be used as a target for therapeutic development to circumvent ABCG2-mediated drug resistance in cancer treatment. [Cancer Res 2007;67(9)4373:–81]
Unravelling the immunomodulatory functions of glucagon like peptide-2 through dendritic cells
Authors: C. T. Tee, D. Bernardo, A. U. Murugananthan, E. R. Mann, S. T. Peake, K. Wallis, S. M. Gabe, S. C. Knight, H. O. Al-Hassi
Journal: Gut (2011)

<h3>Introduction</h3> Animal studies have shown that glucagon like peptide-2 (GLP-2) may reduce mucosal inflammation; it decreases proinflammatory cytokines and ameliorates chronic colitis1. However, we do not yet know whether this anti-inflammatory effect occurs in humans. If so, it potentially opens the door for use of GLP-2 as therapy in conditions like inflammatory bowel disease. Therefore we studied the immunomodulatory functions of GLP-2 in humans. <h3>Methods</h3> Dendritic cells (DC) enriched from human blood of healthy volunteers were cultured <i>in-vitro</i> for 24 h with GLP-2 at concentrations of 1 pM, 1 nM and 1 mM. The effect of GLP-2 on DC survival was determined using apoptosis experiments. Phenotype and functions of DC were then assessed by flow cytometry and mixed leucocyte reaction (MLR), respectively. Each experiment was performed independently at least 3 times and analysed for statistically significant effects. <h3>Results</h3> Apoptosis experiments showed that GLP-2 at all concentrations did not have a toxic effect on DC; their survival after <i>in-vitro</i> culture with GLP-2 was similar to that in basal control culture (p=NS). GLP-2 conditioning changed the phenotype of DC with reduction in HLA-DR intensity (p=0.0243) and increase in CD14 expression (p=0.0237), compared with basal control culture. However, the down-regulation of HLA-DR intensity and up-regulation of CD14 expression did not correlate with an increase in the phagocytic capacity (p=NS). Other markers of immature DC, ILT3 and DC SIGN, were not affected. TLR2/4 expression was also not affected by the treatment (p=NS). Finally, MLR experiments showed that GLP-2 treatment on DC did not have an effect on their stimulation of T cell proliferation (p=NS). <h3>Conclusion</h3> GLP-2 reduced HLA-DR and increased CD14 on DCs, though this effect does not correlate with T-cell stimulation <i>in-vitro</i>. More studies are needed to detect any functional significance to the changes GLP-2 induced on dendritic cells.
HLA-A, B antigens and alpha 1-antitrypsin phenotypes in nodal generalised osteoarthritis and erosive osteoarthritis.
Authors: M Pattrick, A Manhire, A M Ward, M Doherty
Journal: Annals of the Rheumatic Diseases (1989)

<h3>Abstract</h3> Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT<sub>50</sub>) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints. Moderna results were similar to Pfizer at 2 weeks after the second dose, while the titres for AstraZeneca samples derived from older donors were 7-fold lower against VIC31 and below the limit of detection against Delta and Omicron. Age and gender were not found to significantly impact our results. These observations indicate that vaccine matching may be needed, and that at least a third dose of these vaccines is necessary to generate sufficient neutralising antibodies against emerging variants of concern, especially Omicron, amidst the challenges of ensuring vaccine equity worldwide.
Nurse involvement in end-of-life decision making: the ETHICUS Study
Authors: Julie Benbenishty, Freda DeKeyser Ganz, Anne Lippert, Hans-Henrik Bulow, Elisabeth Wennberg, Beverly Henderson, Mia Svantesson, Mario Baras, Dermot Phelan, Paulo Maia, Charles L. Sprung
Journal: Intensive Care Medicine (2005)
Simvastatin in the treatment of asthma: lack of steroid-sparing effect
Authors: D. C. Cowan, J. O. Cowan, R. Palmay, A. Williamson, D. R. Taylor
Journal: Thorax (2010)

<h3>Background</h3> Statins have anti-inflammatory actions which in theory are potentially beneficial in asthma. Small trials have failed to show a significant benefit, but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out. <h3>Methods</h3> A randomised, placebo-controlled, crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred, followed by an increase until regain of control ('minimum' dose required) in 51 patients with asthma and sputum eosinophils (steroid-free) ≥2%. <h3>Results</h3> 43 patients completed the study. There was no significant difference in 'minimum' inhaled corticosteroid (ICS) dose requirement between simvastatin and placebo: (median (IQR) 50 μg daily (0–250) vs 100 μg daily (0–250), p=0.931). 'Minimum' dose distribution was similar (p=0.269). The fluticasone dose at which loss of control occurred did not differ significantly between simvastatin and placebo (p=0.404). In patients with loss of control in both treatment arms, fluticasone dose at loss of control was similar with simvastatin and placebo (median (IQR) 50 μg daily (0–100) for both, p=0.620). In those patients who reached 0 μg/day (n=18), Astma Control Questionnaire (ACQ) was lower (p=0.037), forced expiratory volume in 1 s (FEV<sub>1</sub>) higher (p&lt;0.01) and sputum eosinophils lower with simvastatin compared with placebo (9.5% compared with 25.4%, p=0.033). <h3>Conclusions</h3> Simvastatin does not have clinically important steroid-sparing effects in patients with eosinophilic asthma. In the absence of steroid, simvastatin is associated with minor improvements in symptoms and lung function, and a reduction in sputum eosinophils. <h3>Clinical trial number</h3> ACTRN12606000531516.
Court stands by decision on Gulf war syndrome
Authors: C. Dyer
Journal: BMJ (2003)

The High Court in London refused last week to overturn a ruling that officially recognised for the first time the existence of Gulf war syndrome.

Mr Justice Newman dismissed an appeal by the Ministry of Defence against a decision last year by a war pensions appeal tribunal that Shaun Rusling, a former sergeant in the Parachute Regiment, had the syndrome as a result of his service in the 1991 Gulf war.

However, the judge emphasised that he was not making any ruling on the existence or otherwise of Gulf war syndrome, and the judgment will have no …
Five year follow up of a randomised controlled trial of a stroke rehabilitation unit
Authors: N B Lincoln
Journal: BMJ (2000)

Caring for stroke patients in stroke units, compared with other hospital locations, leads to decreased mortality and disability at one year. 1A trial of a combined acute and rehabilitation ward in Trondheim, Norway, showed that hospital care improved survival and functional outcome at five years. 2 The benefits were attributed to the treatment provided in the first few weeks after stroke.The purpose of this study was to examine the effects of care in a non-acute stroke unit on outcome at five years.
Using Quaternary Structures to Assess the Evolutionary History of Proteins: The Case of the Aspartate Carbamoyltransferase
Authors: B. Labedan
Journal: Molecular Biology and Evolution (2003)

Many evolutionary scenarios describing the history of proteins are based solely on phylogenetic studies. We have designed a new approach that allows ascertainment of such questionable scenarios by taking into account quaternary structures: we used aspartate carbamoyltransferase (ATCase) as a case study. Prokaryotic ATCases correspond to different classes of quaternary structures according to the mode of association of the catalytic PyrB subunit with other polypeptides, either the PyrI regulatory subunit (class B) or a dihydroorotase (class A), which may be active (PyrC, subclass A1) or inactive (PyrC', subclass A2). Class C is uniquely made up of trimers of PyrB. The PyrB phylogenetic tree is not congruent with the tree of life, but it became coherent when we recognized the existence of two families of ATCases, ATC I and ATC II. Remarkably, a very strong correlation was found between the pattern of PyrB phylogenetic clustering and the different classes of quaternary structures of ATCases. All class B ATCases form a clade in family ATC II, which also contains all eukaryotic sequences. In contrast, family ATC I is made up of classes A and C. These results suggest unexpected common ancestry for prokaryotic B and eukaryotic ATCases on the one hand, and for A and C on the other. Thus, the emergence of specific quaternary structures appears to have been a more recent event than the separation into the ATC I and ATC II families. We propose that different evolutionary constraints, depending on the identity of the partners interacting in the different kinds of holoenzymes, operated in a concerted way on the ancestral pyrB genes and the respective associated genes pyrI or pyrC, so as to maintain appropriate inter-polypeptides interactions at the level of quaternary structure. The process of coevolution of genes encoding proteins interacting in various holoenzymes has been assessed by calculating the correlation coefficient between their respective phylogenetic trees. Our approach integrating data obtained from the separate fields of structural biology and molecular evolution could be useful in other cases where pure statistical data need to receive independent confirmation.
Diabetes and Mortality Following Acute Coronary Syndromes
Authors: Sean M. Donahoe, Garrick C. Stewart, Carolyn H. McCabe, Satishkumar Mohanavelu, Sabina A. Murphy, Christopher P. Cannon, Elliott M. Antman
Journal: JAMA (2007)

The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease, the leading cause of death among persons with diabetes. The independent effect of diabetes on mortality following acute coronary syndromes (ACS) is uncertain.To evaluate the influence of diabetes on mortality following ACS using a large database spanning the full spectrum of ACS.A subgroup analysis of patients with diabetes enrolled in randomized clinical trials that evaluated ACS therapies. Patients with ACS in 11 independent Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials from 1997 to 2006 were pooled, including 62,036 patients (46,577 with ST-segment elevation myocardial infarction [STEMI] and 15,459 with unstable angina/non-STEMI [UA/NSTEMI]), of whom 10 613 (17.1%) had diabetes. A multivariable model was constructed to adjust for baseline characteristics, aspects of ACS presentation, and treatments for the ACS event.Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes.Mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with UA/NSTEMI (2.1% vs 1.1%, P < .001) and STEMI (8.5% vs 5.4%, P < .001). After adjusting for baseline characteristics and features and management of the ACS event, diabetes was independently associated with higher 30-day mortality after UA/NSTEMI (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.24-2.56) or STEMI (OR, 1.40; 95% CI, 1.24-1.57). Diabetes at presentation with ACS was associated with significantly higher mortality 1 year after UA/NSTEMI (hazard ratio [HR], 1.65; 95% CI, 1.30-2.10) or STEMI (HR, 1.22; 95% CI, 1.08-1.38). By 1 year following ACS, patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI (7.2% vs 8.1%).Despite modern therapies for ACS, diabetes confers a significant adverse prognosis, which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease.
Carbonyl Reductases: The Complex Relationships of Mammalian Carbonyl- and Quinone-Reducing Enzymes and Their Role in Physiology
Authors: Udo Oppermann
Journal: The Annual Review of Pharmacology and Toxicology (2006)

Carbonyl groups are frequently found in endogenous or xenobiotic compounds. Reactive carbonyls, formed during lipid peroxidation or food processing, and xenobiotic quinones are able to covalently modify DNA or amino acids. They can also promote oxidative stress, the products of which are thought to be an important initiating factor in degenerative diseases or cancer. Carbonyl groups are reduced by an array of distinct NADPH-dependent enzymes, belonging to several oxidoreductase families. These reductases often show broad and overlapping substrate specificities and some well-characterized members, e.g., carbonyl reductase (CBR1) or NADPH-quinone reductase (NQO1) have protective roles toward xenobiotic carbonyls and quinones because metabolic reduction leads to less toxic products, which can be further metabolized and excreted. This review summarizes the current knowledge on structure and function relationships of the major human and mammalian carbonyl reductases identified.
Is Curcumin for Monoclonal Gammopathy of Undetermined Significance without Risk? – Letter
Authors: Alphons J.M. Vermorken, Jingjing Zhu, Willem J.M. Van de Ven
Journal: Clinical Cancer Research (2010)

Comment on: The potential role of curcumin in patients with monoclonal gammopathy of undefined significance--its effect on paraproteinemia and the urinary N-telopeptide of type I collagen bone turnover marker. [Clin Cancer Res. 2009]
Delayed Blanch and Opacity Pulse
Authors: Angus Macmillan
Journal: British Journal of Dermatology (1969)

Journal Article Delayed Blanch and Opacity Pulse Get access Angus Macmillan Angus Macmillan Department of Dermatology, Royal Free Hospital, Gray's Inn Road, London, W.C.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 12, 1 December 1969, Pages 943–944, https://doi.org/10.1111/j.1365-2133.1969.tb15980.x Published: 01 December 1969
Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders
Authors: Susan M. Goebel-Goody, Matthew Baum, Constantinos D. Paspalas, Stephanie M. Fernandez, Niki C. Carty, Pradeep Kurup, Paul J. Lombroso
Journal: Pharmacological Reviews (2011)

Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase that modulates key signaling molecules involved in synaptic plasticity and neuronal function. Targets include extracellular-regulated kinase 1 and 2 (ERK1/2), stress-activated protein kinase p38 (p38), the Src family tyrosine kinase Fyn, <i>N</i>-methyl-d-aspartate receptors (NMDARs), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). STEP-mediated dephosphorylation of ERK1/2, p38, and Fyn leads to inactivation of these enzymes, whereas STEP-mediated dephosphorylation of surface NMDARs and AMPARs promotes their endocytosis. Accordingly, the current model of STEP function posits that it opposes long-term potentiation and promotes long-term depression. Phosphorylation, cleavage, dimerization, ubiquitination, and local translation all converge to maintain an appropriate balance of STEP in the central nervous system. Accumulating evidence over the past decade indicates that STEP dysregulation contributes to the pathophysiology of several neuropsychiatric disorders, including Alzheimer9s disease, schizophrenia, fragile X syndrome, epileptogenesis, alcohol-induced memory loss, Huntington9s disease, drug abuse, stroke/ischemia, and inflammatory pain. This comprehensive review discusses STEP expression and regulation and highlights how disrupted STEP function contributes to the pathophysiology of diverse neuropsychiatric disorders.
Phase III Study of R-CVP Compared With Cyclophosphamide, Vincristine, and Prednisone Alone in Patients With Previously Untreated Advanced Follicular Lymphoma
Authors: Robert Marcus, Kevin Imrie, Philippe Solal-Celigny, John V. Catalano, Anna Dmoszynska, João C. Raposo, Fritz C. Offner, José Gomez-Codina, Andrew Belch, David Cunningham, Elisabeth Wassner-Fritsch, George Stein
Journal: Journal of Clinical Oncology (2008)

To compare the long-term outcome of patients with previously untreated follicular lymphoma (FL) needing therapy, after treatment with cyclophosphamide, vincristine and prednisone (CVP) versus CVP plus rituximab (R-CVP) and to evaluate the predictive value of known prognostic factors after treatment with R-CVP.Patients with previously untreated CD20-positive stage III/IV FL were randomly assigned to eight cycles of R-CVP (n = 159) or CVP alone (n = 162). The median follow-up period was 53 months.The primary end point-time to treatment failure (TTF), which included patients without a response after four cycles as an event-was significantly prolonged in patients receiving R-CVP versus CVP (P < .0001). Improvements in all other end points, including overall and complete response rates (P < .0001), time to progression (TTP; P < .0001), response duration (P < .0001), time to next antilymphoma treatment (P < .0001), and overall survival (OS; P = .029; 4-year OS: 83% v 77%;) were achieved with R-CVP versus CVP alone. Univariate analyses demonstrated an improvement in TTP with R-CVP versus CVP irrespective of the Follicular Lymphoma International Prognostic Index (FLIPI) subgroup, the International Prognostic Index (IPI) subgroup, baseline histology, and the presence or absence of B symptoms or bulky disease. By multivariate analysis, FLIPI retains a strong predictive power for TTP in the presence of the trial treatment effect.Analysis of all outcome measures, including OS, confirm the benefit of adding R to CVP in the front-line treatment of FL.