tbuckley/cabot-search huggingface dataset:
Absence of p21 <sup>Waf1/Cip1/Sdi1</sup> Modulates Macrophage Differentiation and Inflammatory Response and Protects Against Atherosclerosis
Authors: Aksam J. Merched, Lawrence Chan
Journal: Circulation (2004)

Background— The tumor suppressor p53 protects against atherosclerosis progression in several different mouse models. A major target of p53 is p21, the cyclin-dependent kinase inhibitor that regulates entry into the cell cycle of different types of cells, including stem cells. p21 is also involved in the maturation and differentiation of monocytes into macrophages. Methods and Results— We studied the effect of p21 Waf1 inactivation on atherosclerosis development in apolipoprotein E-deficient mice ( apoE − / − ). Contrary to previous data suggesting a protective role for p21, we found that absence of p21, either globally or in bone marrow-derived cells, protects against atherosclerosis. Atherosclerotic lesions of p21 − / − /apoE − / − mice exhibit a more stable phenotype, with increased apoptosis and reduced inflammatory vascular cell adhesion molecule-1 immunostaining but no difference in cellular proliferation compared with lesions of p21 +/+ /apoE − / − mice. Because bone marrow-derived cells mediate many of the effects of p21, we examined the expression profile of 23 genes in macrophages using real-time polymerase chain reaction. Compared with their p21 +/+ counterparts, peritoneal macrophages of p21 − / − mice express lower levels of proinflammatory markers, including macrophage inflammatory proteins 1 and 2 and interleukin-1α, and higher levels of putative protective genes, such as scavenger receptor type B-I and LDL receptor-related protein. Furthermore, we found that, in comparison with p21 +/+ macrophages, p21 − / − macrophages displayed increased phagocytic activity toward fluorescent latex microspheres as well as apoptotic cells, thus uncovering a novel mechanism of the antiinflammatory activity of p21 − / − macrophages. Conclusions— Loss of p21 protects against atherosclerosis in apoE − / − mice. The data underscore the important role of p21 in macrophage function and inflammation and provide insight into the mechanism of the proatherogenic effect of p21.
EFFECT OF NUTRITION ON THE PRODUCTION OF ACUTE DISSEMINATED ENCEPHALOMYELITIS IN MICE
Authors: Howard A. Schneider, Johanna M. Lee, Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1957)

The susceptibility of homozygous BSVS mice to acute disseminated encephalomyelitis (ADE) has been found to be nutritionally dependent. On a laboratory stock regimen of commercial fox chow pellets, whole wheat bread, and milk this genotype is 100 per cent susceptible to the disease. On a "synthetic" diet, containing a minimal list of vitamins adequate for growth and maintenance, susceptibility was found to be reduced to 15 per cent. Supplementation of the "synthetic" diet with biotin, folic acid, and vitamin B12 restored susceptibility to a frequency of 70 per cent. Increasing the supplements tenfold had no further effect in restoring susceptibility frequencies to the 100 per cent level. In the restoration of susceptibility, folic acid and vitamin B12 were equally effective as single supplements and equivalent to the triple vitamin supplement. The effect of single biotin supplementation was less. An outbreak of fatal pasteurellosis among BSVS mice latently infected with Pasteurella and used in an ADE susceptibility test has been described. The fatal pasteurellosis has been ascribed to a constellation of determinants including (a) diet, (b) sex, (c) inoculation events, and (d) latent infection with Pasteurella. With males the susceptible sex it was possible to avert the fatal pasteurellosis and continue the nutritional experiments by using females exclusively.
TFCat: the curated catalog of mouse and human transcription factors
Authors: Debra L Fulton, Saravanan Sundararajan, Gwenael Badis, Timothy R Hughes, Wyeth W Wasserman, Jared C Roach, Rob Sladek
Journal: Genome biology (2009)

Unravelling regulatory programs governed by transcription factors (TFs) is fundamental to understanding biological systems. TFCat is a catalog of mouse and human TFs based on a reliable core collection of annotations obtained by expert review of the scientific literature. The collection, including proven and homology-based candidate TFs, is annotated within a function-based taxonomy and DNA-binding proteins are organized within a classification system. All data and user-feedback mechanisms are available at the TFCat portal http://www.tfcat.ca .
Therapeutic apheresis exchange in two patients with prolidase deficiency
Authors: A. Lupi, B. Casado, M. Soli, M. Bertazzoni, L. Annovazzi, S. Viglio, G. Cetta, P. Iadarola
Journal: British Journal of Dermatology (2002)

Summary BackgroundProlidase deficiency is a rare genetic disorder for which a cure has not yet been found. Objectives To assess the effectiveness of apheresis exchange as a new therapeutic approach. Methods Apheresis exchanges were repeated monthly for four consecutive months, in parallel, on two patients, replacing prolidase-deficient red blood cells with normal filtered cells. Prolidase activity and urinary dipeptides were determined at regular intervals. Results The constant presence of active prolidase inside cells allowed a continuous, although partial, degradation of imidodipeptides, with a concomitant improvement of skin ulceration. Conclusions Apheresis exchange could be a reasonable way of obtaining a clinical improvement in these patients.
Multiple microcrystal deposition disease in a patient with systemic lupus erythematosus.
Authors: M A Rodriguez, H Paul, I Abadi, J R Bravo, P Armas
Journal: Annals of the Rheumatic Diseases (1984)

A 17-year-old female patient with systemic lupus erythematosus (SLE) developed chronic tophaceous gout, chondrocalcinosis and articular capsule calcification in several joints. Analysis of synovial fluid and tophi revealed the coexistence of monosodium urate, calcium pyrophosphate, hydroxyapatite, and cholesterol crystals.
Eribulin: Rediscovering Tubulin as an Anticancer Target
Authors: Antonio Jimeno
Journal: Clinical Cancer Research (2009)

Abstract Eribulin mesylate (E7389) is a synthetic analog of the marine macrolide halichondrin B, which acts as a novel microtubule modulator with a distinct mechanism of action. Two eribulin mesylate phase 1 studies exploring weekly and 3-weekly schedules are reported in this issue. These trials show linear pharmacokinetics, a toxicity profile consisting in neutropenia and fatigue, and early hints of antitumor activity. In this commentary we give a brief historical perspective of the halichondrins and put into context eribulin mesylate as a novel tubulin modulator.
Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease
Authors: C L Sutton
Journal: Gut (2000)

<h3>BACKGROUND</h3> Crohn9s disease is a familial disorder, and antiglycan antibodies to the cell wall mannan of<i>Saccharomyces cerevisiae</i> (ASCA) are highly correlated with Crohn9s disease. <h3>AIMS</h3> To determine whether there is a familial pattern for expression of serum levels of anti-mannan Ig, and whether this trait is expressed in clinically unaffected Crohn9s disease family members. <h3>METHODS</h3> 349 patients with Crohn9s disease, 87 Crohn9s disease affected relatives, 333 inflammatory bowel disease (IBD) free relatives, 58 spouses, and 190 healthy control patients were studied. Serum IgG and IgA binding activity to<i>S cerevisiae</i> cell wall mannan was quantitated by ELISA. <h3>RESULTS</h3> A high percentage of patients with Crohn9s disease (51.9%) and affected family members (56.3%) were seropositive for anti-mannan Ig, compared with the normal control population (3.7%). Seropositive and seronegative phenotypes of Crohn9s disease probands were correlated among all affected relatives, and this association was stronger in affected first degree relatives. Statistical intraclass correlations of quantitative anti-mannan Ig levels revealed significantly less variation within, rather than between families. A significant familial aggregation was observed for affected relatives; this was even stronger for unaffected relatives. While a significant familial aggregation was observed among unaffected siblings pairs, there was no significant correlation among marital pairs. <h3>CONCLUSION</h3> Results show that anti-mannan Ig in family members affected and unaffected with Crohn9s disease is a familial trait for both affected and unaffected relatives. The lack of concordance in marital pairs indicates that familiality is due in part to a genetic factor or childhood environmental exposure.
Acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee: randomised controlled trial
Authors: Jorge Vas, Camila Méndez, Emilio Perea-Milla, Evelia Vega, María Dolores Panadero, José María León, Miguel Ángel Borge, Olga Gaspar, Francisco Sánchez-Rodríguez, Inmaculada Aguilar, Rosario Jurado
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To analyse the efficacy of acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee, with respect to pain relief, reduction of stiffness, and increased physical function during treatment; modifications in the consumption of diclofenac during treatment; and changes in the patient9s quality of life. <b>Design</b> Randomised, controlled, single blind trial, with blinded evaluation and statistical analysis of results. <b>Setting</b> Pain management unit in a public primary care centre in southern Spain, over a period of two years. <b>Participants</b> 97 outpatients presenting with osteoarthritis of the knee. <b>Interventions</b> Patients were randomly separated into two groups, one receiving acupuncture plus diclofenac (n = 48) and the other placebo acupuncture plus diclofenac (n = 49). <b>Main outcome measures</b> The clinical variables examined included intensity of pain as measured by a visual analogue scale; pain, stiffness, and physical function subscales of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index; dosage of diclofenac taken during treatment; and the profile of quality of life in the chronically ill (PQLC) instrument, evaluated before and after the treatment programme. <b>Results</b> 88 patients completed the trial. In the intention to treat analysis, the WOMAC index presented a greater reduction in the intervention group than in the control group (mean difference 23.9, 95% confidence interval 15.0 to 32.8) The reduction was greater in the subscale of functional activity. The same result was observed in the pain visual analogue scale, with a reduction of 26.6 (18.5 to 34.8). The PQLC results indicate that acupuncture treatment produces significant changes in physical capability (P = 0.021) and psychological functioning (P = 0.046). Three patients reported bruising after the acupuncture sessions. <b>Conclusions</b> Acupuncture plus diclofenac is more effective than placebo acupuncture plus diclofenac for the symptomatic treatment of osteoarthritis of the knee.
Feasibility of using subject-collected dust samples in epidemiological and clinical studies of indoor allergens
Authors: M. Sever, S.J. Arbes, B. Vaughn, J. Mehta, J.T. Lynch, H. Mitchell, J.A. Hoppin, H.L. Spencer, D.P. Sandler, D.C. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2005)
Mitochondrial-Mediated Apoptosis in Lymphoma Cells by the Diterpenoid Lactone Andrographolide, the Active Component of <i>Andrographis paniculata</i>
Authors: Shuo Yang, Andrew M. Evens, Sheila Prachand, Amareshwar T.K. Singh, Savita Bhalla, Kevin David, Leo I. Gordon
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Andrographolide is a diterpenoid lactone isolated from Andrographis paniculata (King of Bitters), an herbal medicine used in Asia. It has been reported to have anti-inflammatory, antihypertensive, antiviral, and immune-stimulant properties. Furthermore, it has been shown to inhibit cancer cell proliferation and induce apoptosis in leukemia and solid tumor cell lines. Experimental Design: We studied the Burkitt p53-mutated Ramos cell line, the mantle cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF-1, and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as primary cells from patients with FL, DLBCL, and MCL. Results: We found that andrographolide resulted in dose- and time-dependent cell death as measured by MTT. Andrographolide significantly increased reactive oxygen species (ROS) production in all cell lines. To determine mechanism of cell death, we measured apoptosis by Annexin V/propidium iodide in the presence and absence of the antioxidant N-acetyl-l-cysteine (NAC), the glutathione (GSH)–depleting agent buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was greatly enhanced by BSO, blocked by NAC, and accompanied by poly(ADP-ribose) polymerase cleavage and activation of caspase-3, caspase-8, and caspase-9. We measured BAX conformational change and mitochondrial membrane potential, and using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEFBax−/−/Bak−/−), we found that apoptosis was mediated through mitochondrial pathways, but dependent on caspases in both cell lines and patient samples. Conclusions: Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in primary tumor samples, which was enhanced by depletion of GSH and inhibited by NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid lactones in lymphoma are warranted. Clin Cancer Res; 16(19); 4755–68. ©2010 AACR.
Neuronal death of the cancellation theory?
Authors: Claude Prablanc
Journal: Behavioral and Brain Sciences (1994)

The question of how the brain can construct a stable representation of the external world despite eye movements is a very old one. If there have been some wrong statements of problems (such as the inverted retinal image), other statements are less naive and have led to analytic solutions possibly adopted by the brain to counteract the spurious effects of eye movements. Following the MacKay (1973) objections to the analytic view of perceptual stability, Bridgeman et al. claim that the idea that signals canceling the effects of saccadic eye movements are needed is also a misconception, as is the claim that stability and position encoding are two distinct problems. It must be remembered, however, that what made the theory of “cancellation” formulated by von Holst and Mittelstaedt (1950) so appealing was the clinical observation of perceptual instability following ocular paralysis. Following the concept of corollary discharge, the theory of efference copy had the advantage of simultaneously solving three problems: the stability of the visual world during the saccade, the same visual stability across saccades, and the visual constancy problem of allowing the subject to know where an object in space is.
Heredity in sarcoidosis: a registry-based twin study
Authors: A Sverrild, V Backer, K O Kyvik, J Kaprio, N Milman, C B Svendsen, S F Thomsen
Journal: Thorax (2008)

Sarcoidosis is a multiorgan granulomatous inflammatory disease of unknown aetiology. Familial clustering of cases and ethnic variation in the epidemiology suggests a genetic influence on susceptibility to the disease. This paper reports twin concordance and heritability estimates of sarcoidosis in order to assess the overall contribution of genetic factors to the disease susceptibility.Monozygotic and dizygotic twins enrolled in the Danish and the Finnish population-based national twin cohorts (61,662 pairs in total) were linked to diagnostic information on sarcoidosis obtained from the Danish National Patient Registry or the Social Insurance Institution, Finland registry of reimbursed medication using the 8th and 10th editions of the International Classification of Diseases. The Fisher exact test was used to compare probandwise concordance rates in different zygosity groups. Heritability was estimated based on a multifactorial threshold liability model.A total of 210 twin pairs with at least one proband with a diagnosis of sarcoidosis were identified. The probandwise concordance rate was higher in monozygotic than in dizygotic twins (0.148 vs 0.012). Compared with the general population there was an 80-fold increased risk of developing sarcoidosis in co-twins of affected monozygotic brothers or sisters. The increased risk in dizygotic twins was only 7-fold. Aetiological model fitting gave a heritability of sarcoidosis of 0.66 (95% CI 0.45 to 0.80).This study suggests that genetic factors play an important role in the susceptibility to sarcoidosis. This result should encourage the search for molecular genetic markers of susceptibility to the disease.
Comparison of range of commercial or primary care led weight reduction programmes with minimal intervention control for weight loss in obesity: Lighten Up randomised controlled trial
Authors: K. Jolly, A. Lewis, J. Beach, J. Denley, P. Adab, J. J. Deeks, A. Daley, P. Aveyard
Journal: BMJ (2011)

Objective To assess the effectiveness of a range of weight management programmes in terms of weight loss. Design Eight arm randomised controlled trial. Setting Primary care trust in Birmingham, England. Participants 740 obese or overweight men and women with a comorbid disorder identified from general practice records. Interventions Weight loss programmes of 12 weeks' duration: Weight Watchers; Slimming World; Rosemary Conley; group based, dietetics led programme; general practice one to one counselling; pharmacy led one to one counselling; choice of any of the six programmes. The comparator group was provided with 12 vouchers enabling free entrance to a local leisure (fitness) centre. Main outcome measures The primary outcome was weight loss at programme end (12 weeks). Secondary outcomes were weight loss at one year, self reported physical activity, and percentage weight loss at programme end and one year. Results Follow-up data were available for 658 (88.9%) participants at programme end and 522 (70.5%) at one year. All programmes achieved significant weight loss from baseline to programme end (range 1.37 kg (general practice) to 4.43 kg (Weight Watchers)), and all except general practice and pharmacy provision resulted in significant weight loss at one year. At one year, only the Weight Watchers group had significantly greater weight loss than did the comparator group (2.5 (95% confidence interval 0.8 to 4.2) kg greater loss,). The commercial programmes achieved significantly greater weight loss than did the primary care programmes at programme end (mean difference 2.3 (1.3 to 3.4) kg). The primary care programmes were the most costly to provide. Participants allocated to the choice arm did not have better outcomes than those randomly allocated to a programme. Conclusions Commercially provided weight management services are more effective and cheaper than primary care based services led by specially trained staff, which are ineffective. Trial registration Current Controlled Trials [ISRCTN25072883][1]. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN25072883
Clinical effectiveness of customised sport shoe orthoses for overuse injuries in runners: a randomised controlled study
Authors: A Hirschmüller, H Baur, S Müller, P Helwig, H-H Dickhuth, F Mayer
Journal: British Journal of Sports Medicine (2009)

Background and objectives Treatment of chronic running-related overuse injuries by orthopaedic shoe orthoses is very common but not evidence-based to date. Hypothesis Polyurethane foam orthoses adapted to a participant's barefoot plantar pressure distribution are an effective treatment option for chronic overuse injuries in runners. Design Prospective, randomised, controlled clinical trial. Intervention 51 patients with running injuries were treated with custom-made, semirigid running shoe orthoses for 8 weeks. 48 served as a randomised control group that continued regular training activity without any treatment. Main outcome measures Evaluation was made by the validated pain questionnaire Subjective Pain Experience Scale, the pain disability index and a comfort index in the orthoses group (ICI). Results There were statistically significant differences between the orthoses and control groups at 8 weeks for the pain disability index (mean difference 3.2; 95% CI 0.9 to 5.5) and the Subjective Pain Experience Scale (6.6; 2.6 to 10.6). The patients with orthoses reported a rising wearing comfort (pre-treatment ICI 69/100; post-treatment ICI 83/100) that was most pronounced in the first 4 weeks (ICI 80.4/100). Conclusion Customised polyurethane running shoe orthoses are an effective conservative therapy strategy for chronic running injuries with high comfort and acceptance of injured runners.
An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction
Authors: Andreas D. Niederbichler, Laszlo M. Hoesel, Margaret V. Westfall, Hongwei Gao, Kyros R. Ipaktchi, Lei Sun, Firas S. Zetoune, Grace L. Su, Saman Arbabi, J. Vidya Sarma, Stewart C. Wang, Mark R. Hemmila, Peter A. Ward
Journal: The Journal of Experimental Medicine (2005)

Defective cardiac function during sepsis has been referred to as “cardiomyopathy of sepsis.” It is known that sepsis leads to intensive activation of the complement system. In the current study, cardiac function and cardiomyocyte contractility have been evaluated in rats after cecal ligation and puncture (CLP). Significant reductions in left ventricular pressures occurred in vivo and in cardiomyocyte contractility in vitro. These defects were prevented in CLP rats given blocking antibody to C5a. Both mRNA and protein for the C5a receptor (C5aR) were constitutively expressed on cardiomyocytes; both increased as a function of time after CLP. In vitro addition of recombinant rat C5a induced dramatic contractile dysfunction in both sham and CLP cardiomyocytes, but to a consistently greater degree in cells from CLP animals. These data suggest that CLP induces C5aR on cardiomyocytes and that in vivo generation of C5a causes C5a–C5aR interaction, causing dysfunction of cardiomyocytes, resulting in compromise of cardiac performance.