tbuckley/cabot-search huggingface dataset:
Fractional Exhaled Nitric Oxide Monitoring Does Not Improve Asthma Management in Children with Concordant and Discordant Asthma Phenotypes
Authors: Sandra Voorend-van Bergen, Anja A. Vaessen-Verberne, Anneke M. Landstra, Hein J. Brackel, Norbert J. van den Berg, Peter J. Merkus, Johan C. de Jongste, Mariëlle W. Pijnenburg
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale
Authors: Christopher D Herring, Anu Raghunathan, Christiane Honisch, Trina Patel, M Kenyon Applebee, Andrew R Joyce, Thomas J Albert, Frederick R Blattner, Dirk van den Boom, Charles R Cantor, Bernhard Ø Palsson
Journal: Nature Genetics (2006)
Increased CA 125 in a patient with tuberculous peritonitis: case report and review of published works.
Authors: D K O'Riordan, A Deery, A Dorman, O E Epstein
Journal: Gut (1995)

A case of a middle aged woman with weight loss, ascites, and a pleural effusion is presented where a clinical diagnosis of ovarian cancer was made. Her CA 125 was greatly increased at 873 IU/ml and the ascites was a lymphocytic exudate but cytology failed to show malignant cells. Operative biopsy showed numerous noncaseating granulomas in the omentum but no mycobacterial organisms were seen. Empiric antituberculous treatment was started before positive culture results were received and when treatment had ended both the ascites and pleural effusion had resolved and the CA 125 had fallen to 7 IU/ml. Review of published works showed several other examples of tuberculous peritonitis associated with increased CA 125 and the possible cause of raised CA 125 in this condition is discussed.
2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative
Authors: D. Aletaha, T. Neogi, A. J. Silman, J. Funovits, D. T. Felson, C. O. Bingham, N. S. Birnbaum, G. R. Burmester, V. P. Bykerk, M. D. Cohen, B. Combe, K. H. Costenbader, M. Dougados, P. Emery, G. Ferraccioli, J. M. Hazes, K. Hobbs, T. W. Huizinga, A. Kavanaugh, J. Kay, T. K. Kvien, T. Laing, P. Mease, H. A. Menard, L. W. Moreland, R. L. Naden, T. Pincus, J. S. Smolen, E. Stanislawska-Biernat, D. Symmons, P. P. Tak, K. S. Upchurch, J. Vencovsky, F. Wolfe, G. Hawker
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. <h3>Methods</h3> A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct 'RA'. <h3>Results</h3> In the new criteria set, classification as 'definite RA' is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). <h3>Conclusion</h3> This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct 'RA'.
Clinical and molecular characterisation of hereditary dopamine transporter deficiency syndrome: an observational cohort and experimental study
Authors: Manju A Kurian, Yan Li, Juan Zhen, Esther Meyer, Nebula Hai, Hans-Jürgen Christen, Georg F Hoffmann, Philip Jardine, Arpad von Moers, Santosh R Mordekar, Finbar O'Callaghan, Evangeline Wassmer, Elizabeth Wraige, Christa Dietrich, Timothy Lewis, Keith Hyland, Simon JR Heales, Terence Sanger, Paul Gissen, Birgit E Assmann, Maarten EA Reith, Eamonn R Maher
Journal: The Lancet Neurology (2010)

dopamine transporter deficiency syndrome is the first identified parkinsonian disorder caused by genetic alterations of the dopamine transporter. We describe a cohort of children with mutations in the gene encoding the dopamine transporter (SLC6A3) with the aim to improve clinical and molecular characterisation, reduce diagnostic delay and misdiagnosis, and provide insights into the pathophysiological mechanisms.11 children with a biochemical profile suggestive of dopamine transporter deficiency syndrome were enrolled from seven paediatric neurology centres in the UK, Germany, and the USA from February, 2009, and studied until June, 2010. The syndrome was characterised by detailed clinical phenotyping, biochemical and neuroradiological studies, and SLC6A3 mutation analysis. Mutant constructs of human dopamine transporter were used for in-vitro functional analysis of dopamine uptake and cocaine-analogue binding.children presented in infancy (median age 2·5 months, range 0·5-7) with either hyperkinesia (n=5), parkinsonism (n=4), or a mixed hyperkinetic and hypokinetic movement disorder (n=2). Seven children had been initially misdiagnosed with cerebral palsy. During childhood, patients developed severe parkinsonism-dystonia associated with an eye movement disorder and pyramidal tract features. All children had raised ratios of homovanillic acid to 5-hydroxyindoleacetic acid in cerebrospinal fluid, of range 5·0-13·2 (normal range 1·3-4·0). Homozygous or compound heterozygous SLC6A3 mutations were detected in all cases. Loss of function in all missense variants was recorded from in-vitro functional studies, and was supported by the findings of single photon emission CT DaTSCAN imaging in one patient, which showed complete loss of dopamine transporter activity in the basal nuclei.dopamine transporter deficiency syndrome is a newly recognised, autosomal recessive disorder related to impaired dopamine transporter function. Careful characterisation of patients with this disorder should provide novel insights into the complex role of dopamine homoeostasis in human disease, and understanding of the pathophysiology could help to drive drug development.
Nonconscious processing, anterior cingulate, and catatonia
Authors: Rajendra D. Badgaiyan
Journal: Behavioral and Brain Sciences (2002)

A composite cognitive model of a neuropsychiatric condition should integrate clinical symptoms with the impairments of cognitive information processing. A model of catatonia, for example, should emphasize deficits of nonconscious information processing that impair a patient's ability to use implicit motor feedback for execution and termination of a voluntary motor activity.
Nuclear Gene Variation and Molecular Dating of the Cichlid Species Flock of Lake Malawi
Authors: Yong-Jin Won, Yong Wang, Arjun Sivasundar, Jeremy Raincrow, Jody Hey
Journal: Molecular Biology and Evolution (2006)

The cichlid fishes of Lake Malawi are famously diverse. However, evolutionary studies have been difficult because of their recent and uncertain phylogenetic history. Portions of 12 nuclear loci were sequenced in nine rock-dwelling species (mbuna) and three representatives of pelagic nonmbuna species. In contrast to the pattern of variation at mitochondrial genes, which do provide phylogenetic resolution at the level of mbuna versus nonmbuna, and among some genera, the nuclear loci were virtually devoid of phylogenetic signal. Only a small minority of variable positions were phylogenetically informative, and no phylogenetic branches are supported by more than one site. From the nuclear gene perspective the Malawian radiation appears to be a star phylogeny, as if the founding of the lake was accompanied by a partial bottleneck. The pattern is different from that found in Lake Victoria, in which nuclear loci share large amounts of ancestral variation. In the case of nuclear genes of Lake Malawi, the absence of phylogenetically informative variation suggests a relative absence of ancestral variation. Nuclear genes also differed from the mitochondria in having nearly twice the amount of divergence from Oreochromis (tilapia). An approximate splitting time between mbuna and nonmbuna lineages was estimated as 0.7 Myr. Oreochromis is estimated to have diverged from the cichlids in Lake Malawi and Lake Tanganyika about 18 MYA.
A2.20 The Role of Serum Factors and Toll-Like Receptor Signaling in the Induction of Profibrotic TIMP-1 by Monocytes in Systemic Sclerosis
Authors: Marzena Ciechomska, Christiaan A Huigens, Thomas Hügle, Bridget Griffiths, Timothy RDJ Radstake, Sophie Hambleton, Steven O’Reilly, Jacob M van Laar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Systemic sclerosis (SSc) is an autoimmune disease characterised by fibrosis, vascular dysfunction and abnormal activation of immune cells including monocytes. Monocytes along with fibroblasts play an important role in the production of profibrotic factors such as IL-6 and TIMP-1 (tissue-inhibitor of metalloproteinase-1). TIMPs are specific inhibitors of matrix metalloproteinases (MMPs) regulating extracellular matrix (ECM) turnover. Importantly, the balance between TIMPs and MMPs is altered in most pathological stages including SSc and is associated with abnormal ECM formation. However, the exact factors which drive both profibrotic TIMP-1 secretion are not fully defined. We aim to test whether circulating monocytes from SSc patients produce TIMP-1 in response to TLR activation and serum factors, which contributes to excessive matrix deposition and consequently disease progression. <h3>Materials and Methods</h3> 25 patients with SSc, one IRAK4 deficient patient and 20 HC (healthy control) were included in this study. Peripheral blood monocytes were further separated by CD14+ microbeads. Production of TIMP-1, IL-6 by monocytes was determined by ELISA, qRT-PCR or functional assay in response to either panel of conventional TLR agonists or HC and SSc sera. Skin section from SSc patient was stained with CD14+ and TIMP-1 antibodies and further analysed by confocal microscopy. <h3>Results</h3> TIMP-1 production by monocytes was observed in the SSc skin section and was upregulated in SSc patients compared to HC. Incubation of HC monocytes with SSc sera resulted in functionally active TIMP-1 production. However, pre-treatment with MyD88 inhibitor, but not control peptide, decreased TIMP-1 secretion. Furthermore, SSc-mediated TIMP-1 induction by monocytes was attenuated when FcγR was blocked and also when SSc sera were treated with DNA/RNA endonuclease prior to stimulation. This indicates that SSc sera contain RNA/DNA agonists inducing TIMP-1 production. Indeed, direct treatment of HC and SSc monocytes with a panel of TLR ligands demonstrated strong TIMP-1 and IL-6 production following triggering with TLR8 agonists (ssRNA). TLR8-mediated TIMP-1 production was reduced in monocytes from a patient with a genetic TLR signalling defect or HC monocytes cultured with MyD88 inhibitory peptide. Furthermore, matrix assay of TLR8 stimulated monocytes also confirmed functional TIMP-1 secretion, as matrix metalloproteinase-1 activity was significantly inhibited. <h3>Conclusions</h3> This study indicates a potential link between SSc serum factors and TLR signalling resulting in excessive TIMP-1 secretion by circulating monocytes from SSc patients.
Hyperlipoproteinaemia in primary gout: hyperlipoproteinaemic phenotype and influence of alcohol intake and obesity in Japan.
Authors: S Jiao, K Kameda, Y Matsuzawa, S Tarui
Journal: Annals of the Rheumatic Diseases (1986)

Serum lipoprotein profiles were investigated in 108 male patients with primary gout before treatment to elucidate the prevalence of each individual phenotype of coexisting hyperlipoproteinaemia and pathogenic factors responsible for it. The mean serum triglyceride (TG) and total cholesterol (TC) levels in the patients with gout were 2.10 +/- 0.14 mmol/l and 5.26 +/- 0.10 mmol/l (mean +/- SEM) respectively, which were significantly higher (p less than 0.01 and p less than 0.05 respectively) than the levels in age matched controls without gout (1.30 +/- 0.07 mmol/l and 4.77 +/- 0.08 mmol/l respectively). Serum high density lipoprotein cholesterol (HDL-C) values were slightly decreased in patients with gout compared with controls (1.24 +/- 0.08 mmol/l v 1.40 +/- 0.03 mmol/l, p less than 0.05). Hyperlipoproteinaemia was seen in 61 patients (56%), of whom patients with type IIa, IIb, and IV hyperlipoproteinaemia formed 13, 15, and 69% respectively. Thus the prevalence of type IV hyperlipoproteinaemia was high in primary gout as compared with primary hyperlipoproteinaemia with primary hyperlipoproteinaemia (69% v 43%, p less than 0.01). The independent and relative influences of clinical data of the patients upon the concentrations of serum lipids were assessed by stepwise multiple regression analysis. Two major predictors of serum TG level were alcohol intake (p less than 0.01) and serum uric acid level (p less than 0.05). The most significant predictive variable was alcohol intake, but its influence was judged to be small (r2 = 0.067). None of the other variables, including obesity index, had any significant influence. The relationships between any of these variables and serum TC or HDL-C levels were not significant. In addition, serum lipid levels were investigated in patients with neither obesity (defined as 120% or more of ideal body weight) nor a history of alcohol intake. Their serum TG and TC concentrations were also significantly higher than the respective control levels. Thus hyperlipoproteinaemia in primary gout its unlikely to be secondary to excess alcohol intake or obesity, or both. Instead, it may result from genetic factors such as a combined hyperlipidaemic trait.
The Brainstem and Serotonin in the Sudden Infant Death Syndrome
Authors: Hannah C. Kinney, George B. Richerson, Susan M. Dymecki, Robert A. Darnall, Eugene E. Nattie
Journal: Annual Review of Pathology Mechanisms of Disease (2009)

The sudden infant death syndrome (SIDS) is the sudden death of an infant under one year of age that is typically associated with sleep and that remains unexplained after a complete autopsy and death scene investigation. A leading hypothesis about its pathogenesis is that many cases result from defects in brainstem-mediated protective responses to homeostatic stressors occurring during sleep in a critical developmental period. Here we review the evidence for the brainstem hypothesis in SIDS with a focus upon abnormalities related to the neurotransmitter serotonin in the medulla oblongata, as these are the most robust pathologic findings to date. In this context, we synthesize the human autopsy data with genetic, whole-animal, and cellular data concerning the function and development of the medullary serotonergic system. These emerging data suggest an important underlying mechanism in SIDS that may help lead to identification of infants at risk and specific interventions to prevent death.
Tinea corporis in wrestlers
Authors: Karla Werninghaus
Journal: Journal of the American Academy of Dermatology (1993)

1 entitled, "Tinea Corporis Gladiatorum: An Epidemic of Trichophyton tonsurans in Student Wrestlers".There have been four reported outbreaks and/or epidemics of tinea corporis in wrestlers in the last three decades, three of the four appearing in the past 6 months. 1 -4 Whether the recent surge in publications on this dermatomycosis represents an actual increased incidence or merely an increased awareness remains to be determined.Cohen and Schmidt 2 suggested the term tinea gladiatarum as analogous to the accepted term herpes gladiatarum S , 6 used to describe outbreaks of herpes simplex virus infection in wrestlers.We dislike the term tinea gladiatorum because it is imprecise and not at all analogous to herpes gladiatorum.Herpes refers to a specific genus.The term tinea is much more vague.There is tinea pedis, tinea manuum, tinea cruris, tinea corporis, tinea unguium, and tinea faciale, each of which can be caused by dermatophytes of several genera.There is also tinea versicolor caused by a lipophilic yeast, not a dermatophyte, and tinea amiantacea,7 describing an asbestos-like pattern of scale on the scalp not induced by a fungus.When one uses the term herpes gladiatarum the genus of the infectious agent and fundamental morphology are immediately communicated.On the other hand, tinea gladiatorum communicates less information.All four epidemics of tinea corporis in wrestlers were caused by dermatophytes of the genus Trichophyton: the Swedish epidemic of 1966 by T. verrucosum 3 and the three 1992 reports by T. tonsurans.!' 2, 4 Certainly, the term trichophytosis gladiatorum more precisely describes these epidemics/outbreaks than the disturbingly imprecise tinea gladiatorum.We suggest that the terms tinea gladiatorum and tinea corporis gladiatorum 2 be eliminated to avoid superfluous synonymy.
Peptide vaccination of mice immune to LCMV or vaccinia virus causes serious CD8+ T cell-mediated, TNF-dependent immunopathology
Authors: F. Liu
Journal: Journal of Clinical Investigation (2006)

CD8+ T cells play a key role in clearing primary virus infections and in protecting against subsequent challenge. The potent antiviral effects of these cells make them important components of vaccine-induced immunity and, because of this, peptide vaccines often contain epitopes designed to induce strong CD8+ T cell responses. However, the same effector functions that protect the host also can be harmful if they are not tightly regulated, and virus-specific CD8+ T cells are a frequent cause of immunopathology. Here, we report that the administration of peptide to virus-immune recipient mice can lead to the synchronous activation of preexisting virus-specific CD8+ T cells with serious, and even lethal, consequences. Mice infected with LCMV or vaccinia virus developed rapid and profound hypothermia following injection of cognate synthetic peptides, and LCMV-infected mice frequently died within hours. Detailed analyses of the LCMV infected mice revealed enterocyte apoptosis and implicated TNF produced by peptide-specific CD8+ T cells as the major mediator of disease. The caspase inhibitor zVADfmk had no demonstrable effect on the development of hypothermia, but diminished enterocyte apoptosis and greatly reduced the number of deaths. These findings, if similarly observed in patients, counsel caution when administering powerful immunogens such as peptide vaccines to individuals who may have a large preexisting pool of epitope-specific CD8+ T cells.
The transfer coefficient predicts the endurance increment when oxygen is given in COPD and lung fibrosis
Authors: Dominic Dellweg, Peter Haidl, Brigitte Pape, Dieter Koehler
Journal: European Respiratory Journal (2011)

Background:  Some but not all patients with COPD or interstitial lung disease (ILD) increase their endurance performance when supplemental oxygen is given.   Rationale:  To find parameters that better predict oxygen response.   Method:  We measured the effect of oxygen supplementation on the six-minute walking test performance (6MWD) in 59 COPD and 13 ILD patients. We compiled prediction models by means of multiple stepwise linear regression analysis.   Results:  The percentual change in 6MWD was best predicted by the diffusion capacity, both in COPD (r= -0.43, p=0.0003) and ILD (r=0.75, p=0.001). The same applies for the absolute change in 6MWD in COPD (r= -0.44, p=0.0002) and ILD (r=0.71, p=0.002) patients.   Conclusion:  The diffusion capacity appears to be the single best parameter to predict endurance response to oxygen in COPD and ILD and therefore might be used as a screening tool to select appropriate patients.
A case of a lymphoproliferative disorder: Usefulness of DNA analysis in diagnosis
Authors: S. IDEYAMA, T. TANAKA, M. AKAGI, Y. HORIGUCHI, Y. MIYACHI, S. IMAMURA
Journal: British Journal of Dermatology (1988)

We describe a patient in whom a suppressor/cytotoxic T cell lymphoma was suspected on the basis of histology and immunohistochemistry. DNA analysis of specimens from three different lesions, using restriction enzymes Eco RI and Bam HI, showed the same rearrangement of the T cell receptor β‐chain genes. We consider this technique to be of value in the early diagnosis of malignant lymphoma when differential diagnosis from other lymphoproliferative disorders is difficult with conventional methods.
Ventricular function following experimental coronary artery bypass grafting: the relationship of functional improvement to haemodynamics in the graft
Authors: F. L. ROSENFELDT, C. C. GILL, A. S. WECHSLER, D. C. SABISTON
Journal: Cardiovascular Research (1974)

The effects of myocardial revascularization were studied acutely in 13 dogs with chronic coronary artery occlusion. In nine animals an improvement in ventricular function was demonstrated following revascularization. Functional improvement was generally associated with high flow through the graft and low collateral flow.
Stem cell approaches for diabetes: towards beta cell replacement
Authors: Gordon C Weir, Claudia Cavelti-Weder, Susan Bonner-Weir
Journal: Genome Medicine (2011)

Stem cells hold great promise for pancreatic beta cell replacement therapy for diabetes. In type 1 diabetes, beta cells are mostly destroyed, and in type 2 diabetes beta cell numbers are reduced by 40% to 60%. The proof-of-principle that cellular transplants of pancreatic islets, which contain insulin-secreting beta cells, can reverse the hyperglycemia of type 1 diabetes has been established, and there is now a need to find an adequate source of islet cells. Human embryonic stem cells can be directed to become fully developed beta cells and there is expectation that induced pluripotent stem (iPS) cells can be similarly directed. iPS cells can also be generated from patients with diabetes to allow studies of the genomics and pathogenesis of the disease. Some alternative approaches for replacing beta cells include finding ways to enhance the replication of existing beta cells, stimulating neogenesis (the formation of new islets in postnatal life), and reprogramming of pancreatic exocrine cells to insulin-producing cells. Stem-cell-based approaches could also be used for modulation of the immune system in type 1 diabetes, or to address the problems of obesity and insulin resistance in type 2 diabetes. Herein, we review recent advances in our understanding of diabetes and beta cell biology at the genomic level, and we discuss how stem-cell-based approaches might be used for replacing beta cells and for treating diabetes.