tbuckley/cabot-search huggingface dataset:
Use of Fresh Decellularized Allografts for Pulmonary Valve Replacement May Reduce the Reoperation Rate in Children and Young Adults
Authors: Serghei Cebotari, Igor Tudorache, Anatol Ciubotaru, Dietmar Boethig, Samir Sarikouch, Adelheid Goerler, Artur Lichtenberg, Eduard Cheptanaru, Sergiu Barnaciuc, Anatol Cazacu, Oxana Maliga, Oleg Repin, Liviu Maniuc, Thomas Breymann, Axel Haverich
Journal: Circulation (2011)

Degeneration of xenografts or homografts is a major cause for reoperation in young patients after pulmonary valve replacement. We present the early results of fresh decellularized pulmonary homografts (DPH) implantation compared with glutaraldehyde-fixed bovine jugular vein (BJV) and cryopreserved homografts (CH).Thirty-eight patients with DPH in pulmonary position were consecutively evaluated during the follow-up (up to 5 years) including medical examination, echocardiography, and MRI. These patients were matched according to age and pathology and compared with BJV (n=38) and CH (n=38) recipients. In contrast to BJV and CH groups, echocardiography revealed no increase of transvalvular gradient, cusp thickening, or aneurysmatic dilatation in DPH patients. Over time, DPH valve annulus diameters converge toward normal z-values. Five-year freedom from explantation was 100% for DPH and 86 ± 8% and 88 ± 7% for BJV and CH conduits, respectively. Additionally, MRI investigations in 17 DPH patients with follow-up time >2 years were compared with MRI data of 20 BJV recipients. Both patient groups (DPH and BJV) were at comparable ages (mean, 12.7 ± 6.1 versus 13.0 ± 3.0 years) and have comparable follow-up time (3.7 ± 1.0 versus 2.7 ± 0.9 years). In DPH patients, the mean transvalvular gradient was significantly (P=0.001) lower (11 mm Hg) compared with the BJV group (23.2 mm Hg). Regurgitation fraction was 14 ± 3% and 4 ± 5% in DPH and BJV groups, respectively. In 3 DPH recipients, moderate regurgitation was documented after surgery and remained unchanged in follow-up.In contrast to conventional homografts and xenografts, decellularized fresh allograft valves showed improved freedom from explantation, provided low gradients in follow-up, and exhibited adaptive growth.
Supernormality in Bachmann's Bundle
Authors: R. W. CHILDERS, J. MERIDETH, G. K. MOE
Journal: Circulation Research (1968)

A supernormal phase of conduction between right and left atria was observed in the exposed hearts of anesthetized dogs. Interatrial conduction time of premature atrial responses was reduced by as much as 17% during the early phase of diastole, relative to the conduction interval of basic driven responses. The supernormal phase lasted from 60 to 140 msec and was greater at slower basic driving frequencies. A brief phase of supernormal excitability was also found in the specialized cells of Bachmann's bundle from puppy hearts in vitro. Supernormal conduction was not observed within the atrial appendages (i.e., in areas not supplied by specialized conducting bands); supernormal excitability was not demonstrable in cells of ordinary atrial myocardium. Although vagal stimulation abbreviated transatrial conduction time, atropine did not abolish the phase of supernormality.
SEVERE ACTIVE CUTANEOUS HYPERSENSITIVITY IN THE RAT PRODUCED BY HEMOPHILUS PERTUSSIS VACCINE
Authors: Donald A. Rowley, Jerry Chutkow, Charles Attig
Journal: The Journal of Experimental Medicine (1959)

Hemophilus pertussis vaccine injected into normal rat skin produced local edema lasting several days. Four to 6 days later the injected site became severely inflamed. When uninjected skin was challenged 5 to 28 days after the initial injection, severe inflammation developed at the site of challenge within 12 to 24 hours. This secondary hypersensitive response was elicited by a dose of vaccine which produced little or no initial or delayed inflammation in a normal rat. Specific cutaneous hypersensitivity to a particulate antigen (i.e. typhoid vaccine) or a soluble antigen (human or rabbit gamma globulin) developed when rats were injected with a mixture of the antigen and pertussis vaccine. Pertussis vaccine mixed with typhoid vaccine did not enhance circulating agglutinin formation to typhoid vaccine. Cutaneous hypersensitivity to pertussis vaccine was passively transferred to normal rats by lymph node cells but not with serum from hypersensitive rats. Sensitization with pertussis vaccine did not enhance the edema-producing activity of histamine, serotonin, or 48/80 given subcutaneously. Mast cells in areas of hypersensitive inflammation were not damaged appreciably. The hypersensitive inflammation was not inhibited by treatment with anti-serotonin and antihistaminic drugs. Hypersensitive rats "depleted of mast cells" responded to challenge with pertussis vaccine with severe inflammation though their response to 48/80 was depressed. Hypersensitive rats treated with x-irradiation showed decreased hypersensitive inflammation though they responded normally to 48/80 and histamine. These studies failed to demonstrate a role for circulating antibody in the cutaneous hypersensitive inflammation produced in the rat by pertussis vaccine. Furthermore, the findings indicated that the cutaneous hypersensitive inflammation is not mediated by tissue serotonin and/or histamine.
Altered D-<i>Chiro</i>-Inositol Urinary Clearance in Women With Polycystic Ovary Syndrome
Authors: Jean-Patrice Baillargeon, Evanthia Diamanti-Kandarakis, Richard E. Ostlund, Teimuraz Apridonidze, Maria J. Iuorno, John E. Nestler
Journal: Diabetes Care (2006)

OBJECTIVE—Evidence suggests that some actions of insulin are effected by inositolphosphoglycan (IPG) mediators. We hypothesize that a deficiency in D-chiro-inositol (DCI) and/or a DCI-containing IPG (DCI-IPG) may contribute to insulin resistance in humans. RESEARCH DESIGN AND METHODS—To assess this possibility in polycystic ovary syndrome (PCOS), we determined insulin sensitivity (Si by frequently sampled intravenous glucose tolerance test), plasma and urinary DCI and myo-inositol (MYO) levels (by gas chromatography/mass spectrometry), and the release of insulin and DCI-IPG during the oral glucose tolerance test (area under the curve [AUC]) in 23 women with PCOS and 26 normal women. RESULTS—Women with PCOS were heavier than control subjects (P = 0.002 for BMI), but also had decreased Si (P &amp;lt; 0.001) and increased AUCinsulin (P &amp;lt; 0.001) compared with normal women, even when corrected for BMI. The urinary clearance of DCI (uClDCI) was increased almost sixfold in PCOS compared with normal women (P = 0.001), but not MYO clearance (P = 0.10). uClDCI correlated inversely with Si when all women were analyzed together (n = 49, r = −0.50, P &amp;lt; 0.001) and was one of the three best independent parameters predicting Si. Finally, the ratio of AUCDCI-IPG to AUCinsulin was decreased threefold in women with PCOS (P &amp;lt; 0.001). CONCLUSIONS—uClDCI is inversely correlated with insulin sensitivity in women and is a strong independent predictor of insulin resistance in multivariate models. PCOS, which is characterized by insulin resistance, is associated with a selective increase in uClDCI and impaired DCI-IPG release in response to insulin. These findings are consistent with a defect in tissue availability or utilization of DCI in PCOS that may contribute to the insulin resistance of the syndrome.
Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid arthritis patients with an inadequate response to methotrexate: a randomised, double-blind, placebo-controlled clinical trial
Authors: P. C. Taylor, E. Quattrocchi, S. Mallett, R. Kurrasch, J. Petersen, D. J. Chang
Journal: Annals of the Rheumatic Diseases (2011)

To evaluate the efficacy and safety of intravenous ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, active rheumatoid arthritis (RA) patients despite methotrexate treatment.In this double-blind, placebo-controlled, phase III study, active RA patients on stable methotrexate were randomly assigned to one course of two infusions of ofatumumab 700 mg (n=130) or placebo (n=130), 2 weeks apart. The primary endpoint was the ACR20 response at week 24. Secondary endpoints included ACR50/70, EULAR response, disease activity score based on 28 joints using C-reactive protein, adverse events (AE) and immunogenicity.At week 24, a greater proportion of patients on ofatumumab compared with placebo achieved an ACR20 response (50% vs 27%, p<0.001) and a good or moderate EULAR response (67% vs 41%, p<0.001). All other key secondary efficacy endpoints were significantly improved on ofatumumab. Efficacy observed by 8 weeks was sustained throughout the study. The most common AE for ofatumumab versus placebo were rash (21% vs <1%) and urticaria (12% vs <1%), mostly occurring on the first infusion day. Overall, first-dose infusion reactions were 68% for ofatumumab and 6% for placebo, mostly mild to moderate; second-dose infusion reactions markedly declined (<1% and 0%). Serious AE were reported in 5% of ofatumumab versus 3% of placebo patients. Infection rates were 32% and 26% (serious infections <1% and 2%), respectively. One death (interstitial lung disease), unrelated to study drug, was reported on ofatumumab. No antidrug antibodies were detected in ofatumumab patients.Ofatumumab significantly improved all clinical outcomes in biological-naive, active RA patients with no detectable immunogenicity at week 24. No unexpected safety findings were identified. Trial Registry clinical trials.gov registration number NCT00611455.
Depression and the Course of Coronary Artery Disease
Authors: Alexander H. Glassman, Peter A. Shapiro
Journal: American Journal of Psychiatry (1998)

Literature and folk wisdom have long linked depression and death; however, only recently have scientific studies examined the relation between them. Beginning in the 1970s, investigators compared mortality among patients treated for major depression and the general population. Nine of ten studies found an increased mortality from cardiovascular disease among depressed patients. However, such studies confound the relation between depression and its treatment. Community surveys circumvent this difficulty, but as these studies began to appear, other investigations revealed the strong association between depression and cigarette smoking, which made obvious a need to control for smoking. The first study to do this appeared in 1993, and not only did a relation between depression and mortality persist, but a relation between depression and the development of ischemic disease was revealed. In the past 2 years, six more community surveys have followed populations initially free of disease, and five have observed an increased risk of ischemic heart disease among depressed persons. Another research strategy is to start with subjects who have preexisting cardiovascular disease. Here, too, depression has consistently been associated with a worse outcome. In one well-designed study, patients with depression in the period immediately after a myocardial infarction were 3.5 times more likely to die than nondepressed patients. The basis of this association remains speculative. However, it is likely that the changes in the autonomic nervous system and platelets that are seen in depression account for a substantial portion of the association. (Am J Psychiatry 1998; 155:4–11)
STUDIES ON MEMBRANE-BOUND RECEPTORS FOR ANTIGEN
Authors: Robert D. Stout, Albert H. Coons
Journal: The Journal of Experimental Medicine (1973)

THE EFFECT OF POLYADENYLIC: polyundylic acid complexes (poly A:U) on the amount of antibody on the surface of various populations of mouse lymphoid cells has been investigated by means of a sensitive measure of such activity-the binding by primed cell populations of beta-galactosidase (betaGZ) as an antigen. The sensitivity derives from the liberation of fluorescein from an artificial substrate, fluorescein-di-beta-galactopyranoside (FDbetaG). After incubation with 100 ng/ml of poly A:U, only 40% of the cells previously showing antigen-binding were still active. The optimum range of activity lay between 0.01-1.0 microg/ml poly A:U. Such cells showed increased RNA and protein synthesis as indicated by [(3)H]uridine and [(14)C]amino acid incorporation. The polynucleotide effect was abolished by incubation of the cells with sodium azide or iodoacetate, but not by puromycin. When the proteins on the cell surface were labeled by (125)I, poly A:U caused their release into the medium. Reports by others that the enhancing effect of polynucleotides on the immune response involves the adenylcyclase system are consistent with the finding reported here that reduction of binding by dibutryl 5'-cyclic monophosphoric acid (cAMP) and poly A:U were parallel in extent, and that theophylline and poly A:U acted synergistically in suboptimal concentrations of each.
Maternal use of folic acid supplements during pregnancy, and childhood respiratory health and atopy
Authors: Marga B.M. Bekkers, Liset E.M. Elstgeest, Salome Scholtens, Annemien Haveman-Nies, Johan C. de Jongste, Marjan Kerkhof, Gerard H. Koppelman, Ulrike Gehring, Henriëtte A. Smit, Alet H. Wijga
Journal: European Respiratory Journal (2011)

Previous studies have suggested possible adverse side-effects of maternal use of folic acid-containing supplements (FACSs) during pregnancy on wheeze and asthma in early childhood. We investigated the association between maternal use of FACSs and childhood respiratory health and atopy in the first 8 yrs of life. Data on maternal use of FACSs, collected during pregnancy, were available for 3,786 children participating in the Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Questionnaire data on children’s respiratory and allergic symptoms were collected annually and allergic sensitisation and bronchial hyperresponsiveness (BHR) were measured at 8 yrs of age. No overall (from 1 to 8 yrs of age) associations were observed between maternal use of FACSs and (frequent) asthma symptoms, wheeze, lower respiratory tract infection, frequent respiratory tract infection and eczema. Maternal folic acid use was associated with wheeze at 1 yr of age (prevalence ratio 1.20, 95% CI 1.04–1.39), but not with wheeze at later ages. Pre-natal exposure to FACSs was not associated with sensitisation and BHR. Apart from a small increased risk of early wheeze, we observed no adverse respiratory or allergic outcomes associated with pre-natal FACSs exposure in our study population.
Utilizing whole genome sequences to study population genomics of gene networks: a case study of the Arabidopsis thalianaimmune-signaling network
Authors: Mridu Middha, Yungil Kim, Peter Morrell, Chad Myers, Fumiaki Katagiri
Journal: Genome biology (2011)

Arabidopsis thaliana is a member of the mustard (Brassicaceae) family that is widely used as a model organism in plant biology. The 1001 Genomes Project [1] has been sequencing the genomes of Arabidopsis strains (accessions) and has made these sequences available. We selected the genomes of 30 Arabidopsis accessions with diverse geographical and environmental origins for our analysis. Using the TAIR8 annotation of the Arabidopsis reference genome, for the accession Col-0, we generated a dataset of approximately 27,000 protein-coding genes for all of the 30 genomes. With such population genomic data, it is feasible to ask whether a group of genes is under a different type of selection from the rest of the genome.

The plant immune-signaling network is robust to network perturbations. We hypothesized that genes that constitute a robust network tend to be under neutral selection because deleterious mutations in such genes do not strongly affect the immune phenotype owing to the robustness of the network. We identified the component genes of the plant immune-signaling network in a relatively unbiased manner by mining AraNet [2], which is a functional gene network built without using phenotype information. We compared population genetic summary statistics for the network component genes and those for all of the genes in the genome. For example, Tajima’s D is such a summary statistic, and positive, negative and zero values of Tajima’s D suggest diversifying, purifying and neutral selection, respectively, when the effective population size does not change. The Tajima’s D value distribution for all of the genes in the genome has a single clear peak with a negative value, suggesting that purifying selection is the genomic norm.

Our preliminary results showed that the plant immune-signaling network genes are significantly enriched with genes whose Tajima’s D values are near zero compared with all of the genes in the genome. This finding suggests that there is a lower level of purifying selection among the network component genes than other genes.
Heart rate overshoot in running events.
Authors: K Yamaji, R J Shephard
Journal: British Journal of Sports Medicine (1986)

The phenomenon of heart rate overshoot has been examined in 6 high-school athletes aged 15-16 years and in 8 university athletes aged 19-20 years. The incidence was 100% over distances of 50, 100 and 200 metres, and only one subject failed to show an overshoot following a 400 metre run. However, the overshoot was relatively larger and more long-lived following the shorter runs. While an accumulation of anaerobic metabolites seems the most likely explanation of the phenomenon over the longer distances, in the 50 metre event the Valsalva manoeuvre may also make some contribution.
Interleukin 1 stimulation of collagenase production by cultured fibroblasts.
Authors: A E Postlethwaite, L B Lachman, C L Mainardi, A H Kang
Journal: The Journal of Experimental Medicine (1983)

Interleukin 1 is a monokine that exerts biological effects on a variety of target cells in vitro. In this report, interleukin 1 has been found to be capable of stimulating collagenase production by cultured dermal fibroblasts. The concentrations of interleukin 1 that stimulate fibroblast collagenase production are similar to those that stimulate mouse thymocyte proliferation. Analyses by high performance liquid chromatography indicate that interleukin 1, rather than a contaminating monokine, is responsible for this effect on fibroblasts. Interleukin 1, released in vivo by macrophages infiltrating sites of tissue damage or inflammation, may function to stimulate the release of collagenase by connective tissue fibroblasts.
Cognitive Dysfunction Following Adjuvant Treatment of Breast Cancer: a New Dose-Limiting Toxic Effect?
Authors: Patricia A. Ganz
Journal: JNCI Journal of the National Cancer Institute (1998)

In recognition of the growing number of cancer survivors, the National Cancer Institute (NCI) established the Office of Cancer Survivorship (OCS) in 1996. Research on the late effects of cancer treatment is high on the scientific agenda of the OCS. Somewhat more information is available on the late effects of cancer treatment in children than in adults (1‐6).Research with children has been facilitated by their frequent participation in clinical treatment trials, the high cure rates for many childhood cancers, and the long-term commitment of pediatric oncologists to the follow-up of survivors. Study of the neurocognitive effects of therapy for childhood leukemia has been particularly important because of the targeting of treatment to the central nervous system of patients with this disease (7,8). In contrast, studies of neurocognitive late effects in adults are sparse and have focused primarily on patients receiving cranial irradiation, especially those with small-cell lung cancer (9‐11). In this issue of the Journal, van Dam et al. (12) take an important first step in assessing the prevalence of cognitive dysfunction in women who received adjuvant treatment for highrisk breast cancer. Clinical reports of cognitive changes after high-dose adjuvant therapy for breast cancer prompted this systematic evaluation. The design of the study is important, for it is probably the first to examine comprehensively cognitive functioning in patients with breast cancer within the context of a randomized trial. A further strength is the inclusion of a stage I breast cancer comparison control group that had not received any adjuvant treatment. The use of a disease-specific comparison group permits control for the impact of the diagnosis of cancer on psychologic distress and quality of life (QOL), both of which might affect cognitive functioning. Finally, the use of a battery of standardized neuropsychologic tests with healthy population normative reference data provides another important comparison.
AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective
Authors: James E. Talmadge, Isaiah J. Fidler
Journal: Cancer Research (2010)

Metastasis resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His "seed and soil" hypothesis was substantiated a century later with experimental studies, and numerous reports have confirmed these seminal observations. An improved understanding of the metastatic process and the attributes of the cells selected by this process is critical for the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, so metastasis prevention may not be relevant. Treating systemic disease and identifying patients with early disease should be our goal. Revitalized research in the past three decades has focused on new discoveries in the biology of metastasis. Even though our understanding of molecular events that regulate metastasis has improved, the contributions and timing of molecular lesion(s) involved in metastasis pathogenesis remain unclear. Review of the history of pioneering observations and discussion of current controversies should increase understanding of the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and should lead to the design of successful therapy.
The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1–infected “true” long-term nonprogressors
Authors: Justin Stebbing, Brian Gazzard, Louise Kim, Simon Portsmouth, Adrian Wildfire, Ian Teo, Mark Nelson, Mark Bower, Frances Gotch, Sunil Shaunak, Pramod Srivastava, Steve Patterson
Journal: Blood (2003)