tbuckley/cabot-search huggingface dataset:
Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides
Authors: T. Fujimura, R. Okuyama, Y. Ito, S. Aiba
Journal: British Journal of Dermatology (2008)

It is well known that regulatory T cells (Tregs), identified by their expression of CD4, CD25 and Foxp3, play a crucial role in maintaining peripheral tolerance. Recently, it has been demonstrated that a Treg population resides in normal human skin. However, only a few studies have demonstrated the presence of Foxp3+ Tregs in inflammatory skin disorders.In this study, we immunohistologically examined the presence of CD4+ CD25+ Foxp3+ Tregs in the lesional skin of psoriasis vulgaris, mycosis fungoides and eczematous dermatitis.We used immunohistochemistry to examine the presence of Foxp3+ Tregs in fixed sections of the lesional skin from 16 patients with psoriasis vulgaris, 17 patients with mycosis fungides and 18 patients with eczematous dermatitis in addition to 10 normal skin samples.In normal skin, epidermal and dermal Foxp3+ cells were rare. The psoriasis vulgaris, mycosis fungoides and eczematous dermatitis samples contained substantial numbers of epidermal and dermal CD3+, CD4+ and CD25+ Foxp3+ Tregs. The epidermis contained a higher percentage of CD3+, CD4+ and CD25+ Foxp3+ cells than the dermis. The percentage of Foxp3+ cells among CD3+ or CD4+ cells was significantly lower in eczematous dermatitis than in psoriasis vulgaris or mycosis fungoides, and that of dermal Foxp3+ cells was significantly lower in psoriasis vulgaris than in eczematous dermatitis or mycosis fungoides.The lower percentage of epidermal or dermal Foxp3+ cells in eczematous dermatitis or psoriasis vulgaris, respectively, might contribute to their pathogenesis.
Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy
Authors: Andrew L. Kau, Joseph D. Planer, Jie Liu, Sindhuja Rao, Tanya Yatsunenko, Indi Trehan, Mark J. Manary, Ta-Chiang Liu, Thaddeus S. Stappenbeck, Kenneth M. Maleta, Per Ashorn, Kathryn G. Dewey, Eric R. Houpt, Chyi-Song Hsieh, Jeffrey I. Gordon
Journal: Science Translational Medicine (2015)

Gut bacterial strains targeted by IgA in undernourished Malawian children produce severe enteropathy in gnotobiotic mice and correlate with health status.
An evolutionary perspective on Hebb's reverberatory representations
Authors: David C. Krakauer, Alasdair I. Houston
Journal: Behavioral and Brain Sciences (1995)

Abstract Hebbian mechanisms are justified according to their functional utility in an evolutionary sense. The selective advantage of correlating content-contingent stimuli reflects the putative common cause of temporally or spatially contiguous inputs. The selective consequences of such correlations are discussed by using examples from the evolution of signal form in sexual selection and model-mimic coevolution. We suggest that evolutionary justification might be considered in addition to neurophysiology plansibility when constructing representational models.
Central Obesity, Incident Microalbuminuria, and Change in Creatinine Clearance in the Epidemiology of Diabetes Interventions and Complications Study
Authors: Ian H. de Boer, Shalamar D. Sibley, Bryan Kestenbaum, Joshua N. Sampson, Bessie Young, Patricia A. Cleary, Michael W. Steffes, Noel S. Weiss, John D. Brunzell
Journal: Journal of the American Society of Nephrology (2006)

Weight gain and central obesity are associated with insulin resistance, hypertension, and dyslipidemia in type 1 diabetes. These metabolic abnormalities are risk factors for kidney disease in the general population, but data addressing the relationship of central obesity with kidney disease in type 1 diabetes are limited. Whether waist circumference is associated with incident microalbuminuria and change in creatinine clearance was examined among 1279 participants who had type 1 diabetes and were enrolled in the Epidemiology of Diabetes Interventions and Complications Study, the observational extension of the Diabetes Control and Complications Trial (DCCT). Ninety-three of 1105 participants with normal albumin excretion rate (AER) at DCCT closeout developed incident microalbuminuria over 5.8 yr of follow-up. The hazard ratio for incident microalbuminuria that was associated with each 10-cm greater waist circumference at DCCT closeout was 1.34 (95% confidence interval 1.07 to 1.68), after adjustment for DCCT closeout age, gender, duration of diabetes, treatment group, smoking status, glycosylated hemoglobin, and AER. This increased risk was modestly attenuated when additional adjustment was made for levels of BP and serum lipids. Creatinine clearance declined by an average of 0.34 ml/min per 1.73 m2 each yr over 8 yr of follow-up. Greater rate of decline in creatinine clearance was associated with greater age, conventional insulin therapy during the DCCT, smoking, and greater glycosylated hemoglobin and AER at DCCT closeout but not with waist circumference. In conclusion, waist circumference predicts the subsequent development of microalbuminuria in type 1 diabetes. In contrast, no association of waist circumference with decline in creatinine clearance was observed.
Histone H3.3 Mutations Drive Pediatric Glioblastoma through Upregulation of MYCN
Authors: Lynn Bjerke, Alan Mackay, Meera Nandhabalan, Anna Burford, Alexa Jury, Sergey Popov, Dorine A. Bax, Diana Carvalho, Kathryn R. Taylor, Maria Vinci, Ilirjana Bajrami, Imelda M. McGonnell, Christopher J. Lord, Rui M. Reis, Darren Hargrave, Alan Ashworth, Paul Workman, Chris Jones
Journal: Cancer Discovery (2013)

Abstract Children and young adults with glioblastoma (GBM) have a median survival rate of only 12 to 15 months, and these GBMs are clinically and biologically distinct from histologically similar cancers in older adults. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A, occurring either at or close to key residues marked by methylation for regulation of transcription—K27 and G34. Here, we show that the cerebral hemisphere-specific G34 mutation drives a distinct expression signature through differential genomic binding of the K36 trimethylation mark (H3K36me3). The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem-cell maintenance, cell-fate decisions, and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene that is causative of GBMs when expressed in the correct developmental context. This driving aberration is selectively targetable in this patient population through inhibiting kinases responsible for stabilization of the protein. Significance: We provide the mechanistic explanation for how the first histone gene mutation in human disease biology acts to deliver MYCN, a potent tumorigenic initiator, into a stem-cell compartment of the developing forebrain, selectively giving rise to incurable cerebral hemispheric GBM. Using synthetic lethal approaches to these mutant tumor cells provides a rational way to develop novel and highly selective treatment strategies. Cancer Discov; 3(5); 512–19. ©2013 AACR. See related commentary by Huang and Weiss, p. 484 This article is highlighted in the In This Issue feature, p. 471
Survival and quality of life for patients with COPD or asthma admitted to intensive care in a UK multicentre cohort: the COPD and Asthma Outcome Study (CAOS)
Authors: M J Wildman, C F B Sanderson, J Groves, B C Reeves, J G Ayres, D Harrison, D Young, K Rowan
Journal: Thorax (2008)

Non-invasive ventilation is first-line treatment for patients with acutely decompensated chronic obstructive pulmonary disease (COPD), but endotracheal intubation, involving admission to an intensive care unit, may sometimes be required. Decisions to admit to an intensive care unit are commonly based on predicted survival and quality of life, but the information base for these decisions is limited and there is some evidence that clinicians tend to be pessimistic. This study examined the outcomes in patients with COPD admitted to the intensive care unit for decompensated type II respiratory failure.A prospective cohort study was carried out in 92 intensive care units and 3 respiratory high dependency units in the UK. Patients aged 45 years and older with breathlessness, respiratory failure or change in mental status due to an exacerbation of COPD, asthma or a combination of the two were recruited. Outcomes included survival and quality of life at 180 days.Of the 832 patients recruited, 517 (62%) survived to 180 days. Of the survivors, 421 (81%) responded to a questionnaire. Of the respondents, 73% considered their quality of life to be the same as or better than it had been in the stable period before they were admitted, and 96% would choose similar treatment again. Function during the stable pre-admission period was a reasonable indicator of function reported by those who survived 180 days.Most patients with COPD who survive to 180 days after treatment in an intensive care unit have a heavy burden of symptoms, but almost all of them-including those who have been intubated-would want similar intensive care again under similar circumstances.
The miR-155–PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation
Authors: Dong Lu, Rinako Nakagawa, Sandra Lazzaro, Philipp Staudacher, Cei Abreu-Goodger, Tom Henley, Sara Boiani, Rebecca Leyland, Alison Galloway, Simon Andrews, Geoffrey Butcher, Stephen L. Nutt, Martin Turner, Elena Vigorito
Journal: The Journal of Experimental Medicine (2014)

A single microRNA (miRNA) can regulate the expression of many genes, though the level of repression imparted on any given target is generally low. How then is the selective pressure for a single miRNA/target interaction maintained across long evolutionary distances? We addressed this problem by disrupting in vivo the interaction between miR-155 and PU.1 in mice. Remarkably, this interaction proved to be key to promoting optimal T cell–dependent B cell responses, a previously unrecognized role for PU.1. Mechanistically, miR-155 inhibits PU.1 expression, leading to Pax5 down-regulation and the initiation of the plasma cell differentiation pathway. Additional PU.1 targets include a network of genes whose products are involved in adhesion, with direct links to B–T cell interactions. We conclude that the evolutionary adaptive selection of the miR-155–PU.1 interaction is exercised through the effectiveness of terminal B cell differentiation.
Comparison of the American-European Consensus Group Sjögren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort
Authors: Astrid Rasmussen, John A Ice, He Li, Kiely Grundahl, Jennifer A Kelly, Lida Radfar, Donald U Stone, Kimberly S Hefner, Juan-Manuel Anaya, Michael Rohrer, Rajaram Gopalakrishnan, Glen D Houston, David M Lewis, James Chodosh, John B Harley, Pamela Hughes, Jacen S Maier-Moore, Courtney G Montgomery, Nelson L Rhodus, A Darise Farris, Barbara M Segal, Roland Jonsson, Christopher J Lessard, R Hal Scofield, Kathy L Moser Sivils
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Abstract</h3> <h3>Objective</h3> To compare the performance of the American–European Consensus Group (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjögren9s Syndrome (SS) in a well-characterised sicca cohort, given ongoing efforts to resolve discrepancies and weaknesses in the systems. <h3>Methods</h3> In a multidisciplinary clinic for the evaluation of sicca, we assessed features of salivary and lacrimal gland dysfunction and autoimmunity as defined by tests of both AECG and ACR criteria in 646 participants. Global gene expression profiles were compared in a subset of 180 participants. <h3>Results</h3> Application of the AECG and ACR criteria resulted in classification of 279 and 268 participants with SS, respectively. Both criteria were met by 244 participants (81%). In 26 of the 35 AECG+/ACR participants, the minor salivary gland biopsy focal score was ≥1 (74%), while nine had positive anti-Ro/La (26%). There were 24 AECG−/ACR+ who met ACR criteria mainly due to differences in the scoring of corneal staining. All patients with SS, regardless of classification, had similar gene expression profiles, which were distinct from the healthy controls. <h3>Conclusions</h3> The two sets of classification criteria yield concordant results in the majority of cases and gene expression profiling suggests that patients meeting either set of criteria are more similar to other SS participants than to healthy controls. Thus, there is no clear evidence for increased value of the new ACR criteria over the old AECG criteria from the clinical or biological perspective. It is our contention, supported by this report, that improvements in diagnostic acumen will require a more fundamental understanding of the pathogenic mechanisms than is at present available.
The effect of exposure to sulphuric acid on the early asthmatic response to inhaled grass pollen allergen
Authors: W.S. Tunnicliffe, D.E. Evans, D. Mark, R.M. Harrison, J.G. Ayres
Journal: European Respiratory Journal (2001)

Particulate sulphates, including sulphuric acid (H 2 SO 4 ), are important components of the ambient aerosol in some areas and are regarded as air pollutants with potentially important human health effects. Challenge studies suggest little or no effect of H 2 SO 4 exposure on lung function in asthmatic adults, although some epidemiological studies demonstrate an effect of acid species on symptoms in subjects with asthma. To date, the effect of H 2 SO 4 on allergen responsiveness has not been studied. The effect of exposure to particulate H 2 SO 4 on the early asthmatic response to grass pollen allergen has been investigated in 13 adults with mild asthma. After establishment of the provocative dose of allergen producing a 15% fall in forced expiratory volume in one second (FEV 1 ) (PD 15 ) for each subject, they were exposed to air, 100 µg·m −3 or 1,000 g·m −3 H 2 SO 4 for 1 h, double-blind in random order ≥2 weeks apart, through a head dome delivery system 14 h after each exposure subject underwent a fixed-dose allergen challenge (PD 15 ). Ten subjects completed the study. The mean early asthmatic responses (maximum percentage change in FEV 1 during the first 2 h after challenge) following air, 100 µg·m −3 H 2 SO 4 , and 1,000 µg·m −3 H 2 SO 4 , were −14.1%, −16.7%, and −18.4%, respectively. The difference between 1,000 µg·m −3 H 2 SO 4 and air was significant (mean difference: −4.3%, 95% confidence interval (CI: −1.2–−7.4%, p=0.013). The difference between air and 100 µg·m −3 H 2 SO 4 approached significance (mean difference: −2.6%, 95% CI: 0.0–−5.3%, p=0.051). These results suggest that, at least at high mass concentration, sulphuric acid can potentiate the early asthmatic response of mild asthmatic subjects to grass pollen allergen, although the effect is limited.
Defective macrophage phagocytosis of bacteria in COPD
Authors: A. E. Taylor, T. K. Finney-Hayward, J. K. Quint, C. M. R. Thomas, S. J. Tudhope, J. A. Wedzicha, P. J. Barnes, L. E. Donnelly
Journal: European Respiratory Journal (2009)

Exacerbations of chronic obstructive pulmonary disease (COPD) are an increasing cause of hospitalisations and are associated with accelerated progression of airflow obstruction. Approximately half of COPD exacerbations are associated with bacteria and many patients have lower airways colonisation. This suggests that bacterial infection in COPD could be due to reduced pathogen removal. This study investigated whether bacterial clearance by macrophages is defective in COPD. Phagocytosis of fluorescently labelled polystyrene beads and Haemophillus influenzae and Streptococcus pneumoniae by alveolar macrophages and monocyte-derived macrophages (MDM) was assessed by fluorimetry and flow cytometry. Receptor expression was measured by flow cytometry. Alveolar macrophages and MDM phagocytosed polystyrene beads similarly. There was no difference in phagocytosis of beads by MDM from COPD patients compared with cells from smokers and nonsmokers. MDM from COPD patients showed reduced phagocytic responses to S. pneumoniae and H. influenzae compared with nonsmokers and smokers. This was not associated with alterations in cell surface receptor expression of toll-like receptor (TLR)2, TLR4, macrophage receptor with collagenous structure, cluster of differentiation (CD)163, CD36 or mannose receptor. Budesonide, formoterol or azithromycin did not suppress phagocytosis suggesting that reduced responses in COPD MDM were not due to medications. COPD macrophage innate responses are suppressed and may lead to bacterial colonisation and increased exacerbation frequency.
Relationship between gastric localization of HCV and gastric, H. pylori-related lymphoid tissue
Authors: G. Cammarota, R. Cianci, L.M. Larocca, F. Pandolfi, A. Gasbarrini, R.L. Grillo, M. Pompili, G. Pignataro, C. Di Campli, M. Vastola, G. Gasbarrini
Journal: Journal of Hepatology (2001)
Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women.
Authors: T J Powles, T Hickish, J A Kanis, A Tidy, S Ashley
Journal: Journal of Clinical Oncology (1996)

PURPOSE Tamoxifen is an effective treatment for metastatic and primary breast cancer and is now being evaluated as a chemoprevention agent in healthy women. Any long-term effects on estrogen-sensitive tissues such as bone may have important therapeutic implications. METHODS We measured bone mineral density (BMD) in the lumbar spine and hip using dual-energy x-ray absorptiometry (DXA) in premenopausal and postmenopausal healthy women who participated in our placebo-controlled tamoxifen chemoprevention of breast cancer trial. RESULTS BMD data are now available from 179 women for this analysis. In premenopausal women, BMD decreased progressively in the lumbar spine (P &lt; .001) and in the hip (P &lt; .05) for women on tamoxifen, but not those on placebo. The mean annual loss in lumbar BMD per year over the 3-year study period in tamoxifen-treated compliant women who remained premenopausal throughout the study period was 1.44% (1.88% calculated on an intent-to-treat basis) compared with a small gain of 0.24% per annum for women on placebo (P &lt; .001). Tamoxifen had the opposite effect in postmenopausal women. The mean annual increase in BMD for women on tamoxifen was 1.17% in the spine (P &lt; .005) and 1.71% in the hip (P &lt; .001) compared with a noninsignificant loss for women on placebo. CONCLUSION These results indicate that tamoxifen treatment is associated with a significant loss of BMD in premenopausal women, whereas it prevents bone loss in postmenopausal women. These adverse and beneficial effects of tamoxifen should be considered in the assessment of the therapeutic benefits for both the adjuvant treatment and the chemoprevention of breast cancer.
A Lecture on Bougies, their Use and Abuse
Authors: F. S. Edwards
Journal: BMJ (1885)

July 1 1 i ea],TRR RBRITISH MRDP1AWTOVR.NtAY.6Of history of cancer; and I quite agree with Mr. Cripps that, where only two members of the same family are attacked by cancer, they ought to be nearly related, and that we ought to be cognisant of a very
Nephritis-Associated Plasmin Receptor and Acute Poststreptococcal Glomerulonephritis
Authors: Nobuyuki Yoshizawa, Kazuo Yamakami, Masayuki Fujino, Takashi Oda, Kikuko Tamura, Koichi Matsumoto, Tetsuzo Sugisaki, Michael D.P. Boyle
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The role of nephritis-associated antigen as a virulence factor for acute poststreptococcal glomerulonephritis (APSGN) remains to be fully clarified. Nephritis-associated plasmin receptor (NAPlr) was previously isolated from group A streptococcus (GAS) and shown to bind plasmin(ogen). The nucleotide sequence of the naplr gene from GAS isolates obtained from patients with APSGN was determined. The sequence of the putative open reading frame (1011 bp) showed 99.8% identity among isolated strains. Homology screen revealed an exact match with streptococcal glyceraldehyde-3-phosphate dehydrogenase (GAPDH). NAPlr exhibited GAPDH activity in zymography, and it activated the complement pathway in vitro. In APSGN kidney biopsy specimens, NAPlr was observed mainly in the early stage of the disease (1 to 14 d after onset) but was not colocalized with either C3 or IgG as assessed by double immunofluorescence staining. Sera of patients with APSGN, patients with GAS infection without renal involvement, nonrenal pediatric patients, and healthy adults as controls were assayed for anti-NAPlr antibody titers. Anti-NAPlr antibodies were present most frequently in APSGN sera, and antibody titers were also significantly higher than in patients with GAS infection alone or in other control patients. Moreover, antibody titers remained elevated during the entire 10-yr follow-up period.
Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison
Authors: Christos Pantelis, Dennis Velakoulis, Patrick D McGorry, Stephen J Wood, John Suckling, Lisa J Phillips, Alison R Yung, Edward T Bullmore, Warrick Brewer, Bridget Soulsby, Patricia Desmond, Philip K McGuire
Journal: The Lancet (2003)
Severe hyponatremia is a better predictor of mortality than MELDNa in patients with cirrhosis and refractory ascites
Authors: Thomas Sersté, Thierry Gustot, Pierre-Emmanuel Rautou, Claire Francoz, Hassane Njimi, Francois Durand, Dominique Valla, Didier Lebrec, Richard Moreau
Journal: Journal of Hepatology (2012)
Muscle and Joint Function in Human Locomotion
Authors: Marcus G. Pandy, Thomas P. Andriacchi
Journal: Annual Review of Biomedical Engineering (2010)

This review describes how computational modeling can be combined with noninvasive gait measurements to describe and explain muscle and joint function in human locomotion. Five muscles—the gluteus maximus, gluteus medius, vasti, soleus, and gastrocnemius—contribute most significantly to the accelerations of the center of mass in the vertical, fore-aft, and medio-lateral directions when humans walk and run at their preferred speeds. Humans choose to switch from a walk to a run at speeds near 2 m s −1 to enhance the biomechanical performance of the ankle plantarflexors and to improve coordination of the knee and ankle muscles during stance. Muscles that do not span a joint can contribute to the contact force transmitted by that joint and therefore affect its stability. In walking, for example, uniarticular muscles that cross the hip and ankle act to create the adduction moment at the knee, thereby contributing to the contact force present in the medial compartment.
The Attitudes of Patients and Aides Toward the Role of the Psychiatric Aide
Authors: LEONARD HANDLER, GERALD PERLMAN
Journal: American Journal of Psychiatry (1973)

It has been difficult to evolve a system whereby psychiatric aides can be effectively selected and oriented to their roles. In an attempt to involve the patient in an evaluation of the aide's role, the authors interviewed 80 patients as well as 40 aides. Regarding the aide's function, patients were significantly more concerned than aides with humanistic, as opposed to custodial, values. "Humanistic" aides were evaluated significantly more favorably by patients than were "custodial" aides.