tbuckley/cabot-search huggingface dataset:
The role of L3T4 in recognition of Ia by a cytotoxic, H-2Dd-specific T cell hybridoma.
Authors: J L Greenstein, J Kappler, P Marrack, S J Burakoff
Journal: The Journal of Experimental Medicine (1984)

The expression of T4/T8 surface markers on human T cells and of L3T4/Lyt-2 on murine T cells has lead to the association of these surface markers with recognition of either class II or class I major histocompatibility complex (MHC) antigens. It has been suggested that these T cell surface antigens interact with MHC antigens. We have examined the role of L3T4 in the recognition of Dd by the T cell hybridoma, 3DT52.5. This T cell hybridoma was found to be specific for the N/Cl domain of Dd. The recognition of a class I antigen by an Lyt-2-, L3T4+ T cell hybridoma allowed the separate evaluation of interactions between L3T4/Ia and the T cell antigen receptor, Dd. Recognition by this hybridoma resulted in the production of interleukin 2 (IL-2) and cytolytic activity. Antibody blocking experiments have demonstrated that L3T4 was involved in triggering the effector function of 3DT52.5 only on Ia+ stimulator or target cells. We have demonstrated that an L3T4+, Dd-specific T cell hybridoma, 3DT52.5, uses the L3T4 molecule to directly interact with nonpolymorphic Ia determinants.
Human piRNAs Are Under Selection in Africans and Repress Transposable Elements
Authors: S. Lukic, K. Chen
Journal: Molecular Biology and Evolution (2011)

Piwi-interacting RNAs (piRNAs) are a recently discovered class of 24- to 30-nt noncoding RNAs whose best-understood function is to repress transposable elements (TEs) in animal germ lines. In humans, TE-derived sequences comprise ∼45% of the genome and there are several active TE families, including LINE-1 and Alu elements, which are a significant source of de novo mutations and intrapopulation variability. In the "ping-pong model," piRNAs are thought to alternatively cleave sense and antisense TE transcripts in a positive feedback loop. Because piRNAs are poorly conserved between closely related species, including human and chimpanzee, we took a population genomics approach to study piRNA function and evolution. We found strong statistical evidence that piRNA sequences are under selective constraint in African populations. We then mapped the piRNA sequences to human TE sequences and found strong correlations between the age of each LINE-1 and Alu subfamily and the number of piRNAs mapping to the subfamily. This result supports the idea that piRNAs function as repressors of TEs in humans. Finally, we observed a significant depletion of piRNA matches in the reverse transcriptase region of the consensus human LINE-1 element but not of the consensus mouse LINE-1 element. This result suggests that reverse transcriptase might have an endogenous role specific to humans. Overall, our results elucidate the function and evolution of piRNAs in humans and highlight the utility of population genomics analysis for studying this rapidly evolving genetic system.
The number and distribution of benign pigmented moles (melanocytic naevi) in a healthy British population
Authors: R.M. MACKIE, J. ENGLISH, T.C. AITCHISON, C.P. FITZSIMONS, P. WILSON
Journal: British Journal of Dermatology (1985)

Total body mole counts have been performed on 432 normal healthy Caucasian subjects aged 4 days to 96 years (204 males and 228 females). The mean total body mole count in the first decade of life is three for females and two for males, rising rapidly in the second decade to a mean of 23 for females and 18 for males. In the third decade numbers are highest, with a mean of 33 for females and 22 for males. Thereafter, numbers of moles slowly drop until in the eighth decade they have fallen to levels similar to those seen in pre-pubertal children. There is a significant association between the presence of naevi in early childhood (prior to 5 years of age) and the development in later life of large numbers of moles. In women there is no significant association between total mole counts and either parity or use of the oral contraceptive.
Prophylactic heparin in palliative care: A cautious welcome…
Authors: Victor Pace, Emma Hal, Catherine Bailey
Journal: BMJ (2006)

EDITOR—Although we agree with the conclusions of the survey reported by Noble et al of patients' views on receiving low molecular weight heparin in palliative care, we wish to sound some notes of caution.1 Reasons other than preciousness about patients' comfort lie behind a reluctance to give many patients in palliative care prophylactic treatment with low molecular weight heparin.

In advanced cancer …
L- and P-Selectin and CD11/CD18 in Intracapillary Neutrophil Sequestration in Rabbit Lungs
Authors: HIROSHI KUBO, NICHOLAS A. DOYLE, LORI GRAHAM, SABRINA D. BHAGWAN, WILLIAM M. QUINLAN, CLAIRE M. DOERSCHUK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Infusion of complement fragments induces rapid sequestration of neutrophils within pulmonary capillaries. This study examined the mechanisms through which this sequestration occurs, as well as the effect of complement fragments on the expression of L-selectin and CD11/CD18 using ultrastructural immunohistochemistry. Studies using anti-P-selectin antibodies, fucoidin, L-selectin-depleted neutrophils, and anti-CD18 antibodies showed that selectins and CD18 were not required for neutrophil sequestration. However, maintaining the sequestered neutrophils within the pulmonary capillaries required both L-selectin and CD11/CD18. Neutrophils in the pulmonary capillaries of rabbits given complement fragments expressed 72% less L-selectin and 98% more CD11/CD18 than did those in rabbits given saline. Shedding of L-selectin occurred preferentially from the microvillar processes of the plasma membrane rather than from the flat intervening regions. About 28% of L-selectin still remained on intracapillary neutrophil membranes after 15 min and was likely available for binding. Shedding of L-selectin appeared slower in vivo than in vitro. These studies indicate that neutrophil sequestration induced by complement fragments requires at least two sequential steps, one that does not require recognized adhesion molecules followed by a second that requires L-selectin and CD11/ CD18.
Phrenic neuropathy in chronic renal failure.
Authors: U Zifko, M Auinger, G Albrecht, T Kastenbauer, H Lahrmann, W Grisold, T Wanke
Journal: Thorax (1995)

Peripheral neuropathy and alterations in diaphragmatic muscle function are frequently caused by uraemia. Phrenic nerve function in patients with end stage renal failure, however, has not been examined to date.An electrophysiological study of the phrenic nerve was performed to determine its possible involvement in 32 nondiabetic patients with end stage renal disease undergoing chronic haemodialysis.Seventeen patients had electrophysiological signs of peripheral neuropathy in at least one of the investigated nerves and 14 of the 17 showed pathological phrenic nerve latencies. Delayed phrenic nerve latencies correlated clearly with pathological peroneal nerve conduction velocities.Phrenic neuropathy is a frequent complication of uraemia.
Splenomegaly, anaemia and pleural effusion
Authors: P Kojodjojo
Journal: Journal of the Royal Society of Medicine (2005)

3 Miwa K, Kambara H, Kawai C. Variant angina aggravated by aspirin.Lancet 1979;2:13824 Habbab MA, Szwed SA, Haft JI. Is coronary arterial spasm part of theaspirin-induced asthma syndrome? Chest 1986;90:141–35 Kontos MC, Jesse RL, Tatum JL, Ornato JP. Coronary angiographicﬁndings in patients with cocaine-induced chest pain. J Emerg Med2003;24:9–13
Comparison of an Insulin Analog, Insulin Aspart, and Regular Human Insulin With No Insulin in Gestational Diabetes Mellitus
Authors: David J. Pettitt, Paulina Ospina, Jerzey W. Kolaczynski, Lois Jovanovic
Journal: Diabetes Care (2003)

OBJECTIVE—To assess the short-term efficacy of insulin aspart in comparison with regular human insulin in women with gestational diabetes mellitus (GDM) during standardized meal tests. RESEARCH DESIGN AND METHODS—The study included 15 women with GDM who had inadequate diabetes control with diet alone. On 3 consecutive days, breakfast meal tests were performed—the first with no exogenous insulin and the other two after the injection of either regular insulin or insulin aspart. RESULTS—The peak insulin concentration was higher and the peak glucose and C-peptide concentrations were lower with both insulin preparations than with no exogenous insulin. Glucose areas under the curve above baseline were significantly lower with insulin aspart (180-min area, 7.1 mg · h · dl−1; P = 0.018), but not with regular insulin (30.2 mg · h · dl−1; P = 0.997), than with no insulin (29.4 mg · h · dl−1). CONCLUSIONS—This study demonstrates that effective postprandial glycemic control in women with GDM who required insulin was brought about by insulin aspart through higher insulin peak and lower demand on endogenous insulin secretion.
Heat-stable antigen is a costimulatory molecule for CD4 T cell growth.
Authors: Y Liu, B Jones, A Aruffo, K M Sullivan, P S Linsley, C A Janeway
Journal: The Journal of Experimental Medicine (1992)

Optimal induction of clonal expansion by normal CD4 T cells requires a ligand that can engage the T cell receptor as well as functionally defined costimulatory activity on the same antigen-presenting cell surface. While the presence of effective costimulation induces proliferation, T cell receptor ligation in its absence renders T cells inactive or anergic. The molecular basis of this costimulatory activity remains to be defined. Here we describe a monoclonal antibody that can block the costimulatory activity of splenic accessory cells. Treatment with this antibody not only blocks the proliferation of CD4 T cells to a T cell receptor ligand, but also induces T cell nonresponsiveness to subsequent stimulation. Sequence analysis of the antigen recognized by this antibody indicates that it recognizes a protein that is identical to heat-stable antigen. Gene transfer experiments directly demonstrate that this protein has costimulatory activity. Thus, heat-stable antigen meets the criteria for a costimulator of T cell clonal expansion.
Strong Purifying Selection at Genes Escaping X Chromosome Inactivation
Authors: C. Park, L. Carrel, K. D. Makova
Journal: Molecular Biology and Evolution (2010)

To achieve dosage balance of X-linked genes between mammalian males and females, one female X chromosome becomes inactivated.However, approximately 15% of genes on this inactivated chromosome escape X chromosome inactivation (XCI).Here, using a chromosome-wide analysis of primate X-linked orthologs, we test a hypothesis that such genes evolve under a unique selective pressure.We find that escape genes are subject to stronger purifying selection than inactivated genes and that positive selection does not significantly affect the evolution of these genes.The strength of selection does not differ between escape genes with similar versus different expression levels in males versus females.Intriguingly, escape genes possessing Y homologs evolve under the strongest purifying selection.We also found evidence of stronger conservation in gene expression levels in escape than inactivated genes.We hypothesize that divergence in function and expression between X and Y gametologs is driving such strong purifying selection for escape genes.
The effect of<i>FTO</i>variation on increased osteoarthritis risk is mediated through body mass index: a mendelian randomisation study
Authors: Kalliope Panoutsopoulou, Sarah Metrustry, Sally A Doherty, Laura L Laslett, Rose A Maciewicz, Deborah J Hart, Weiya Zhang, Kenneth R Muir, Margaret Wheeler, Cyrus Cooper, Tim D Spector, Flavia M Cicuttini, Graeme Jones, Nigel K Arden, Michael Doherty, Eleftheria Zeggini, Ana M Valdes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> Variation in the fat mass and obesity-associated (<i>FTO</i>) gene influences susceptibility to obesity. A variant in the <i>FTO</i> gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the <i>FTO</i> polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. <h3>Methods</h3> 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the <i>FTO</i> variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the <i>FTO</i> variant as the instrumental variable to evaluate the role of overweight on OA. <h3>Results</h3> In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10<sup>−7</sup>). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. <h3>Conclusions</h3> Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the <i>FTO</i> gene and supports the causative role of high BMI in OA.
Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses
Authors: Bogdan Calenic, Maria Greabu, Constantin Caruntu, Cristiana Tanase, Maurizio Battino
Journal: Periodontology 2000 (2015)

Abstract Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self‐renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor‐cell subpopulations have been categorized based on combinations of positive and/or negative membrane‐surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self‐renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem‐cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem‐cell‐derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry.
UDCA, PBC and biochemistry: what does normal mean?
Authors: K D LINDOR
Journal: Gut (2000)

See article on page 121 

In this issue (see page 121), Lueschner and colleagues extend previous reports regarding factors that predict biochemical normalisation in patients with primary biliary cirrhosis (PBC) being treated with ursodeoxycholic acid (UDCA).1 This study differs from others in having a much longer follow up period, an unusually large percentage of patients with early stage disease, and intensive evaluation during the follow up, including extensive biochemical, immunoserological, tumour marker, HLA typing, and histological evaluations.

They found, perhaps not surprisingly, that the less abnormal the tests initially, the more likely they were to become normal eventually on treatment and, perhaps even more obviously, the patients who had the best response after one year of treatment were most likely to have test values within the normal range when follow up was extended. They also noted histological improvement and the suggestion that symptoms improve in those patients in whom biochemical tests return to normal. …
Systematic reviews and meta-analyses on treatment of asthma: critical evaluation
Authors: A. R Jadad
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the clinical, methodological, and reporting aspects of systematic reviews and meta-analyses on the treatment of asthma and to compare those published by the Cochrane Collaboration with those published in paper based journals. <b>Design:</b> Analysis of studies identified from Medline, CINAHL, HealthSTAR, EMBASE, <i>Cochrane Library</i>, personal collections, and reference lists. <b>Studies:</b> Articles describing a systematic review or a meta-analysis of the treatment of asthma that were published as a full report, in any language or format, in a peer reviewed journal or the <i>Cochrane Library</i>. <b>Main outcome measures:</b> General characteristics of studies reviewed and methodological characteristics (sources of articles; language restrictions; format, design, and publication status of studies included; type of data synthesis; and methodological quality). <b>Results:</b> 50 systematic reviews and meta-analyses were included. More than half were published in the past two years. Twelve reviews were published in the <i>Cochrane Library</i> and 38 were published in 22 peer reviewed journals. Forced expiratory volume in one second was the most frequently used outcome, but few reviews evaluated the effect of treatment on costs or patient preferences. Forty reviews were judged to have serious or extensive flaws. All six reviews associated with industry were in this group. Seven of the 10 most rigorous reviews were published in the <i>Cochrane Library</i>. <b>Conclusions:</b> Most reviews published in peer reviewed journals or funded by industry have serious methodological flaws that limit their value to guide decisions. Cochrane reviews are more rigorous and better reported than those published in peer reviewed journals.
A trial of caspofungin salvage treatment in PCP pneumonia
Authors: D. Armstrong-James, J. Stebbing, L. John, A. Murungi, M. Bower, B. Gazzard, M. Nelson
Journal: Thorax (2010)

Pneumocystis jirovecii pneumonia (PCP) remains a major cause of mortality in patients with HIV; we read with enormous interest the recent PCP mortality prediction rule stratifying 451 patients by mortality at the time of illness presentation.1 The first-line treatment for this infection, cotrimoxazole, is associated with a number of adverse effects, including rash, leucopenia, thrombocytopenia and interstitial nephritis.2 Therefore, treatment with cotrimoxazole significantly adds to the morbidity associated with this condition and we note in this study that this was the main treatment used.

One of the identifying characteristics of P jirovecii is the presence of (1,3)-β-d-glucan in its cell wall.3 As the cell wall of this organism does not contain ergosterol (the target of azoles and polyenes), echinocandins, which target the synthesis of (1,3)-β-d-glucan, are likely to be the only effective antifungals for PCP.4

Caspofungin was the first echinocandin licensed for empiric antifungal treatment in candidiasis and aspergillosis. In animal …
Safety and Efficacy of Teduglutide After 52 Weeks of Treatment in Patients With Short Bowel Intestinal Failure
Authors: Stephen J.D. O'Keefe, Palle B. Jeppesen, Richard Gilroy, Marek Pertkiewicz, Johane P. Allard, Bernard Messing
Journal: Clinical Gastroenterology and Hepatology (2013)
Methodological issues in evaluating measures of health as outcomes for COPD
Authors: P.W. Jones, R.M. Kaplan
Journal: European Respiratory Journal (2003)

The selection of an appropriate outcome measure depends on the aspect of the disease being addressed and the purpose of the study being conducted. The most fundamental property of any outcome is its ability to measure the biological variable under question. Other properties such as discriminative and evaluative abilities are also important. Specific outcomes measure a single biological variable, such as forced expiratory volume in one second or depression. The specificity of such measures is attractive but requires precise definition of what is being measured and why. Other, summative, outcomes are used to quantify the overall effect of a number of different biological processes. The simplest summative measures are global questions such as “How would you rate your health overall?” Others are complex with many items. If designed and used correctly, these questionnaires can provide an estimate of the overall impact of disease or response to therapy and an index of whether that response was clinically worthwhile. Standardisation of measurements is important to permit comparisons between patients and studies, which makes the measurement of an individual9s “quality of life” difficult. The term “health-status measurement” may be better when referring to the use of standardised questionnaires. Utility-based measures help address concerns regarding clinical <i>versus</i> statistical improvement and place outcomes for chronic obstructive pulmonary disease treatment trials in the context of all healthcare treatments.
Respiratory symptoms and lung function in young adults with severe alpha1-antitrypsin deficiency (PiZZ)
Authors: E Piitulainen
Journal: Thorax (2002)

<b>Background:</b> Neonatal screening for alpha<sub>1</sub>–antitrypsin (AAT) deficiency was undertaken in Sweden between 1972 and 1974 when 129 infants with severe AAT deficiency (phenotype PiZ) were identified. The cohort has been followed up prospectively. <b>Methods:</b> 124 PiZ subjects, still alive and still living in Sweden, were invited to a follow up examination at about 22 years of age. The check up included a clinical examination, spirometric tests, and a questionnaire on smoking habits and respiratory symptoms. <b>Results:</b> Ninety eight subjects (97 PiZZ and 1 PiZ–) subjects attended the follow up. The mean age of the subjects was 22.5 years (range 19.8–24.8). The mean (SD) forced expiratory volume in 1 second (FEV<sub>1</sub>) was 98 (14)% predicted, vital capacity (VC) was 103 (14)% predicted, and the mean FEV<sub>1</sub>/VC ratio was 83 (7)%. Eighty six subjects had previously undergone spirometric tests. The median follow up time was 4.3 years (range 0.9–7.3). The mean annual change in FEV<sub>1</sub> (% predicted) was –1.2% (95% CI –2.1 to –0.3), in VC (% predicted) was –1.5% (95% CI –2.0 to –0.9), and in the FEV<sub>1</sub>/VC ratio (%) was –0.3% (95% CI –0.7 to 0.2). Twenty eight individuals (29%) reported recurrent wheezing. Fifteen subjects (15%) had been diagnosed by a physician as having asthma. Eighteen subjects reported that they had smoked at some time; 10 were current smokers. The mean number of pack years among the ever smokers was 3.4 (range 0.6–10.5). Ten of 18 ever-smokers and 18 of 80 non-smokers reported recurrent wheezing (p&lt;0.01), while exertional dyspnoea was reported by six ever smokers and 11 non-smokers (p&lt;0.05). Lung function test results did not differ significantly between ever smokers and non-smokers. <b>Conclusions:</b> Young PiZ adults have essentially normal lung function, but have a high prevalence of asthma symptoms. Smoking in these individuals is associated with an increased frequency of respiratory symptoms.