tbuckley/cabot-search huggingface dataset:
T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice.
Authors: N J Davidson, M W Leach, M M Fort, L Thompson-Snipes, R Kühn, W Müller, D J Berg, D M Rennick
Journal: The Journal of Experimental Medicine (1996)

Mice rendered deficient in the production of interleukin 10 (IL-10-/-) develop a chronic inflammatory bowel disease (IBD) that predominates in the colon and shares histopathological features with human IBD. Our aim was to identify which cell type(s) can mediate colitis in IL-10-/- mice. We detected an influx of immunoglobulin-positive cells into the colon and the presence of colon-reactive antibodies in the serum of IL-10-/- mice. To assess a pathogenic role for B cells, we generated a B cell-deficient (B-/-) strain of IL-10-/- mice. B-/-IL-10-/- mice acquired a severe colitis analogous to that IL-10-/- mice, implying that B cells were not the primary mediator of IBD in this model. A series of cell transfer experiments was performed to assess a pathogenic role for T cells. When IL-10-/- T cell-enriched lamina propria lymphocytes (LPL) or intraepithelial lymphocytes (IEL) were transferred into immunodeficient recombinase-activating gene (RAG)-2-/- recipients, a mild to severe colitis developed, depending on the cell number transferred. Lymphocytes recovered from the colon of transplanted RAG-2-/- mice with colitis were predominantly alpha beta TCR+CD4+, including a large proportion of CD4+CD8 alpha + cells. These cells were also CD45RB-/low and CD44+, indicative of an activated/memory population. Individual populations of CD4+CD8 alpha-, CD4+CD8 alpha + and CD4-CD8 alpha + T cells were then isolated from the lamina propria compartment of IL-10-/- mice and transferred into RAG-2-/- recipients. Only IL-10-/- CD4-expressing LPL, including both the CD4+CD8 alpha- and CD4+CD8 alpha + populations, induced colitis in recipient mice. Interferon-gamma, but little to no IL-4, was produced by CD4+CD8 alpha- and CD4+CD8 alpha + LPL recovered from the inflamed colons of RAG-2-/- recipients implicating alpha T helper cell 1 (TH1)-mediated response. We thus conclude that colitis in IL-10-/- mice is predominantly mediated by TH1-type alpha beta TCR+ T cells expressing CD4 alone, or in combination with the CD8 alpha molecule.
THU0314 Altered White Matter Integrity in Corpus Callosal Area in Fibromyalgia Identified with Tract Based Spatial Statistical Analysis
Authors: H.A. Kim, D. Kim, K.M. Son, C.-K. Chung
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Although recent imaging studies of fibromyalgia (FM) have converged on a dysfunction of central pain processing as a primary pathophysiology of the disorder, microstructural alteration suggestive of abnormal synaptic transmission or functional activation has not been extensively examined. <h3>Objectives</h3> We aimed to investigate white matter integrity and its possible relationship with pain symptoms in female subjects with FM. <h3>Methods</h3> Nineteen FM patients and age-, and gender-, and education-matched 21 healthy controls (HCs) were included and underwent diffusion-weighted imaging. Group difference in white matter integrity, assessed via fractional anisotropy (FA), was investigated by applying tract-based spatial statistics. <h3>Results</h3> FM group showed a single cluster with lower FA in the left body of corpus callosum, which was found to be connected with the bilateral sensorimotor cortices, compared with HCs corrected for multiple comparisons (<i>P</i>&lt;0.05). Furthermore, FA values in the resulting cluster were negatively associated with sensory pain as measured by the short-form McGill Pain Questionnaire, and also with relative magnitude of sensory pain vs. affective pain (calculated by sensory score/affective score). <h3>Conclusions</h3> In summary, the current study demonstrated that patients with FM had disrupted white matter microstructure in the body of corpus callosum associated with clinical pain intensity. Our results suggest that abnormal interhemispheric transfer might contribute to heightened pain perception and further strengthen the hypothesis of centrally augmented pain processing in FM. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4736
Amyloid-β and Tau
Authors: George S. Bloom
Journal: JAMA Neurology (2014)

The defining features of Alzheimer disease (AD) include conspicuous changes in both brain histology and behavior. The AD brain is characterized microscopically by the combined presence of 2 classes of abnormal structures, extracellular amyloid plaques and intraneuronal neurofibrillary tangles, both of which comprise highly insoluble, densely packed filaments. The soluble building blocks of these structures are amyloid-β (Aβ) peptides for plaques and tau for tangles. Amyloid-β peptides are proteolytic fragments of the transmembrane amyloid precursor protein, whereas tau is a brain-specific, axon-enriched microtubule-associated protein. The behavioral symptoms of AD correlate with the accumulation of plaques and tangles, and they are a direct consequence of the damage and destruction of synapses that mediate memory and cognition. Synapse loss can be caused by the failure of live neurons to maintain functional axons and dendrites or by neuron death. During the past dozen years, a steadily accumulating body of evidence has indicated that soluble forms of Aβ and tau work together, independently of their accumulation into plaques and tangles, to drive healthy neurons into the diseased state and that hallmark toxic properties of Aβ require tau. For instance, acute neuron death, delayed neuron death following ectopic cell cycle reentry, and synaptic dysfunction are triggered by soluble, extracellular Aβ species and depend on soluble, cytoplasmic tau. Therefore, Aβ is upstream of tau in AD pathogenesis and triggers the conversion of tau from a normal to a toxic state, but there is also evidence that toxic tau enhances Aβ toxicity via a feedback loop. Because soluble toxic aggregates of both Aβ and tau can self-propagate and spread throughout the brain by prionlike mechanisms, successful therapeutic intervention for AD would benefit from detecting these species before plaques, tangles, and cognitive impairment become evident and from interfering with the destructive biochemical pathways that they initiate.
Rotator cuff tendinopathy
Authors: J S Lewis
Journal: British Journal of Sports Medicine (2008)

Purpose: A review was conducted to synthesise the available research literature on the pathogenesis of rotator cuff tendinopathy. Relevance: Musculoskeletal disorders of the shoulder are extremely common, with reports of prevalence ranging from one in three people experiencing shoulder pain at some stage of their lives to approximately half the population experiencing at least one episode of shoulder pain annually. Pathology of the soft tissues of the shoulder, including the musculotendinous rotator cuff and subacromial bursa, is a principal cause of pain and suffering. Conclusions: The pathoaetiology of rotator cuff failure is multifactorial and results from a combination of intrinsic, extrinsic and environmental factors. The specialised morphology of the rotator cuff, together with the effects of stress shielding, may contribute to the development of rotator cuff tendinopathy. Profound changes within the subacromial bursa are strongly related to the pathology and resulting symptoms. A considerable body of research is necessary to more fully understand the aetiology and pathohistology of rotator cuff tendinopathy and its relationship with bursal pathology. Once this knowledge exists more effective management will become available.
Respiratory muscle fibres: specialisation and plasticity
Authors: B Polla
Journal: Thorax (2004)

Skeletal muscles are composed of fibres of different types, each type being identified by the isoform of myosin heavy chain which is expressed as slow 1, fast 2A, fast 2X, and fast 2B. Slow fibres are resistant to fatigue due to their highly oxidative metabolism whereas 2X and 2B fibres are easily fatiguable and fast 2A fibres exhibit intermediate fatigue resistance. Slow fibres and fast fibres are present in equal proportions in the adult human diaphragm while intercostal muscles contain a higher proportion of fast fibres. A small fibre size, abundance of capillaries, and a high aerobic oxidative enzyme activity are typical features of diaphragm fibres and give them the resistance to fatigue required by their continuous activity. Because of their fibre composition, intercostal muscles are less resistant to fatigue. The structural and functional characteristics of respiratory muscle fibres are not fixed, however, and can be modified in response to several physiological and pathological conditions such as training (adaptation to changes in respiratory load), adaptation to hypoxia, age related changes, and changes associated with respiratory diseases. The properties of respiratory muscle fibres can also be modified by pharmacological agents such as β<sub>2</sub> agonists and corticosteroids used for the treatment of respiratory diseases.
Involvement of tumor necrosis factor in endotoxin-triggered neutrophil adherence to sinusoidal endothelial cells of mouse liver and its modulation in acute phase
Authors: H.-J. Schlayer, H. Laaff, T. Peters, M. Woort-Menker, H.C. Estler, U. Karck, H.E. Schaefer, K. Decker
Journal: Journal of Hepatology (1988)
Randomized Controlled Trial of Contingency Management for Stimulant Use in Community Mental Health Patients With Serious Mental Illness
Authors: Michael G. McDonell, Debra Srebnik, Frank Angelo, Sterling McPherson, Jessica M. Lowe, Andrea Sugar, Robert A. Short, John M. Roll, Richard K. Ries
Journal: American Journal of Psychiatry (2013)

The primary objective of this study was to determine whether contingency management was associated with increased abstinence from stimulant drug use in stimulant-dependent patients with serious mental illness treated in a community mental health center. Secondary objectives were to determine whether contingency management was associated with reductions in use of other substances, psychiatric symptoms, HIV risk behavior, and inpatient service utilization.A randomized controlled design was used to compare outcomes of 176 outpatients with serious mental illness and stimulant dependence. Participants were randomly assigned to receive 3 months of contingency management for stimulant abstinence plus treatment as usual or treatment as usual with reinforcement for study participation only. Urine drug tests and self report, clinician-report, and service utilization outcomes were assessed during the 3-month treatment period and the 3-month follow-up period.Although participants in the contingency management condition were significantly less likely to complete the treatment period than those assigned to the control condition (42% compared with 65%), they were 2.4 times (95% CI=1.9–3.0)more likely to submit a stimulant-negative urine test during treatment. Compared with participants in the control condition,they had significantly lower levels of alcohol use, injection drug use, and psychiatric symptoms and were one-fifth as likely as those assigned to the control condition to be admitted for psychiatric hospitalization during treatment. They also reported significantly fewer days of stimulant drug use during the 3-month follow-up.When added to treatment as usual, contingency management is associated with large reductions in stimulant,injection drug, and alcohol use.Reductions in psychiatric symptoms and hospitalizations are important secondary benefits.
Non-Hodgkin's lymphoma in systemic lupus erythematosus
Authors: S Bernatsky
Journal: Annals of the Rheumatic Diseases (2005)

Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL).To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL.A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined.42 cases of NHL occurred in the patients with SLE during the 76,948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis.These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.
Autologous Transplantation of Granulocyte Colony–Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes
Authors: Gian Paolo Fadini, Angelo Avogaro
Journal: Diabetes Care (2006)

Huang et al. (1), in their small seminal clinical trial of cellular therapy for critical limb ischemia in diabetic patients, did not include presence of diabetic retinopathy among their exclusion criteria. It is known that individuals with diabetes are subjected to poor blood vessel growth in ischemic hearts and limbs and increased angiogenesis in retinal complications. This so-called “diabetic paradox” has been attributed …
Rib cage mechanics after median sternotomy.
Authors: T J Locke, T L Griffiths, H Mould, G J Gibson
Journal: Thorax (1990)

A substantial reduction in lung volumes occurs after sternotomy, but the mechanism or mechanisms are unclear. Measurements were made of lung volumes and of chest wall motion with four pairs of magnetometers (two pairs for anteroposterior rib cage, one for lateral rib cage, and one for anteroposterior abdominal dimensions) in 16 men before and one week and three months after coronary artery grafting. Reductions in all lung volumes occurred after sternotomy and were greater in the supine than in the sitting position. Supine vital capacity was reduced one week after surgery, with almost complete recovery at three months. One week after sternotomy there was a significant reduction in tidal volume from a mean (95% confidence limits) value of 0.88 (0.76-1.00) litre to 0.61 (0.52-0.70) l, and in supine rib cage displacement from 3.87 (1.96-5.78) mm to 0.44 (-0.61-1.49) mm in the lateral plane. Respiratory frequency increased from 16 (13-19) to 21 (19-24)/min. Coordination of the rib cage was assessed by measuring the difference in timing of onset of chest wall motion and airflow in four planes. At one week nine of 14 patients showed uncoordination between airflow and rib cage motion in one or more dimensions, and this was still present in three patients at three months. No loss of the temporal relation between airflow and abdominal wall motion was detected. The results suggest that reduced and uncoordinated rib cage expansion contributes to the restrictive ventilatory defect that follows median sternotomy.
<i>Demodex</i>quantification methods: limitations of confocal laser scanning microscopy
Authors: N. Lacey, F.M.N. Forton, F.C. Powell
Journal: British Journal of Dermatology (2013)

Funding sources: None. Conflicts of interest: None declared. Madam, We read with interest the recent paper by Sattler et al.1 describing the quantification of Demodex mites using confocal laser scanning microscopy (CLSM). Their work is interesting but we feel that there are limitations to the use of this method for accurately detecting absolute numbers of mites in human skin. Because the role of Demodex in normal or diseased skin is unknown,2 and because of their possible role in modulation of immune reactivity of the follicle3 and an association between the degree of mite infestation and the development of rosacea,4 5 6 the need for accurate reproducible in vivo methods of quantifying mites is becoming increasingly important. Demodex folliculorum and Demodex brevis are most numerous in the sebaceous follicles of the central facial skin of humans. The upper portion and infundibulum of the sebaceous follicle appear to be populated almost entirely by mature adult D. folliculorum (some of which are dead). Histological sections of skin show that mites are orientated with their cephalic portion downwards in the follicular canal and their vermiform opisthosoma upwards protruding into the follicular ostium. Figure 1 in the publication by Sattler et al. nicely shows the opisthosoma of several mites within the infundibulum of a follicle. Figure 2 in their article is unclear, as the 'lengthy cone‐shaped body' of Demodex 'cut sideways' is not apparent to these authors.
Evolutionary Constraint and Adaptation in the Metabolic Network of Drosophila
Authors: A. J. Greenberg, S. R. Stockwell, A. G. Clark
Journal: Molecular Biology and Evolution (2008)

Organisms must carefully control their metabolism in order to survive. On the other hand, enzymes must adapt in response to evolutionary pressures on the pathways in which they are imbedded. Taking advantage of the newly available whole-genome sequences of 12 Drosophila species, we examined how protein function and metabolic network architecture influence rates of enzyme evolution. We found that despite high overall constraint, there were significant differences in rates of amino acid substitution among functional classes of enzymes. This heterogeneity arises because proteins involved in the metabolism of foreign compounds evolve relatively rapidly, whereas enzymes that act in "core" metabolism exhibit much slower rates of amino acid replacement, suggesting strong selective constraint. Network architecture also influences enzymes' rates of amino acid replacement. In particular, enzymes that share metabolites with many other enzymes are relatively constrained, although apparently not because they are more likely to be essential. Our analyses suggest that this pattern is driven by strong constraint of enzymes acting at branch points in metabolic pathways. We conclude that metabolic network architecture and enzyme function separately affect enzyme evolution rates.
Coronary Flow Velocity Pattern and Coronary Flow Reserve by Contrast-Enhanced Transthoracic Echocardiography Predict Long-Term Outcome in Heart Transplantation
Authors: Francesco Tona, Alida L.P. Caforio, Roberta Montisci, Antonio Gambino, Annalisa Angelini, Massimo Ruscazio, Giuseppe Toscano, Giuseppe Feltrin, Angelo Ramondo, Gino Gerosa, Sabino Iliceto
Journal: Circulation (2006)

We assessed coronary flow velocity pattern and coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) as markers of major adverse cardiac events (MACE) related to cardiac allograft vasculopathy (CAV) after heart transplantation (HT).Deceleration time of diastolic flow velocity (DDT) and CFR were measured in the left anterior descending coronary artery (LAD) by CE-TTE in 66 consecutive HT patients (follow-up 19+/-5 months). CFR was calculated as the ratio of hyperemic to basal diastolic flow velocity. Angiographies were analyzed by a qualitative grading system; CAV was defined as changes grade II or higher. MACE were cardiac death, stent implantation, and heart failure. Patients with MACE had higher CAV incidence (P=0.004) and grade (P=0.008), shorter DDT (P=0.006), and lower CFR (P=0.008). A receiver-operating characteristic-derived DDT cutpoint < or = 840 ms (area under the curve 0.793; P=0.01) was 75% specific and 86% sensitive for predicting MACE, with positive predictive value (PPV) and negative predictive value (NPV) of 33% and 97%, respectively (P=0.002). A CFR cutpoint of < or =2.6 (area under the curve 0.746; P=0.01) was 62% specific and 91% sensitive for predicting MACE (PPV =32%, NPV =97%) (P=0.001). Patients with CFR < or = 2.6 and patients with DDT < or = 840 ms had a lower survival free from MACE (P=0.006 and P=0.009, respectively). By Cox regression, only a lower CFR predicted the risk of MACE (relative risk 3.1; 95% CI, 1.26 to 7.9; P=0.01).In HT patients, shorter DDT and lower CFR by CE-TTE are reliable markers for CAV-related MACE. CFR is the main independent predictor of MACE.
Benign Recurrent Intrahepatic Cholestasis: Failure of S–Adenosylmethionine Therapy
Authors: Harold O. Conn, C. N. Ghent
Journal: Hepatology (1990)

S –Adenosylmethionine (800 mg i.v. per day) was used to treat two brothers and a brother and sister from each of two kindreds with benign recurrent intrahepatic cholestasis. Symptoms, routine tests of liver function, concentrations of total bile acids, and the oral clearances of [11,12– 2 H]chenodeoxycholic acid and [24– 13 C]cholic acid were determined before and after treatment with S –adenosylmethionine. S –Adenosylmethionine did not ameliorate symptoms or biochemical parameters of cholestasis but reduced bile acid clearances in 3 of 4 subjects. Transaminase levels in both subjects of one kindred rose during treatment. These limited, preliminary observations suggest that S –adenosylmethionine may be ineffective in the therapy of benign recurrent intrahepatic cholestasis and may be hepatotoxic in some patients.
Role of self-carriers in the immune response and tolerance. I. B-cell unresponsiveness and cytotoxic T-cell immunity induced by haptenated syngeneic lymphoid cells.
Authors: D W Scott, C A Long
Journal: The Journal of Experimental Medicine (1976)

Normal spleen cells cultured with TNP-modified syngeneic spleen cells fail to mount an anti-TNP PFC response to TNP-ficoll or TNP-red blood cells,but go on to generate cytotoxic T cells directed at hapten-modified H-2.These results suggest that hapten-modifeid spleen cells may differentially induce B-cell tolerance and T- (Ly 2,3) cell immunity. The differential response to modified self by lymphocyte subpopulations is discussed.
Reconstructing Genealogies of Serial Samples Under the Assumption of a Molecular Clock Using Serial-Sample UPGMA
Authors: Alexei Drummond, Allen G. Rodrigo
Journal: Molecular Biology and Evolution (2000)

Reconstruction of evolutionary relationships from noncontemporaneous molecular samples provides a new challenge for phylogenetic reconstruction methods. With recent biotechnological advances there has been an increase in molecular sequencing throughput, and the potential to obtain serial samples of sequences from populations, including rapidly evolving pathogens, is fast being realized. A new method called the serial-sample unweighted pair grouping method with arithmetic means (sUPGMA) is presented that reconstructs a genealogy or phylogeny of sequences sampled serially in time using a matrix of pairwise distances. The resulting tree depicts the terminal lineages of each sample ending at a different level consistent with the sample's temporal order. Since sUPGMA is a variant of UPGMA, it will perform best when sequences have evolved at a constant rate (i.e., according to a molecular clock). On simulated data, this new method performs better than standard cluster analysis under a variety of longitudinal sampling strategies. Serial-sample UPGMA is particularly useful for analysis of longitudinal samples of viruses and bacteria, as well as ancient DNA samples, with the minimal requirement that samples of sequences be ordered in time.