tbuckley/cabot-search huggingface dataset:
Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils
Authors: Alexandra Belus, Nicoletta Piroddi, Cecilia Ferrantini, Chiara Tesi, Olivier Cazorla, Luana Toniolo, Maurice Drost, Giulia Mearini, Lucie Carrier, Alessandra Rossi, Alessandro Mugelli, Elisabetta Cerbai, Jolanda van der Velden, Corrado Poggesi
Journal: Circulation Research (2010)

Chronic atrial fibrillation (cAF) is associated with atrial contractile dysfunction. Sarcomere remodeling may contribute to this contractile disorder.Here, we use single atrial myofibrils and fast solution switching techniques to directly investigate the impact of cAF on myofilament mechanical function eliminating changes induced by the arrhythmia in atrial myocytes membranes and extracellular components. Remodeling of sarcomere proteins potentially related to the observed mechanical changes is also investigated.Myofibrils were isolated from atrial samples of 15 patients in sinus rhythm and 16 patients with cAF. Active tension changes following fast increase and decrease in [Ca(2+)] and the sarcomere length-passive tension relation were determined in the 2 groups of myofibrils. Compared to sinus rhythm myofibrils, cAF myofibrils showed (1) a reduction in maximum tension and in the rates of tension activation and relaxation; (2) an increase in myofilament Ca(2+) sensitivity; (3) a reduction in myofibril passive tension. The slow beta-myosin heavy chain isoform and the more compliant titin isoform N2BA were up regulated in cAF myofibrils. Phosphorylation of multiple myofilament proteins was increased in cAF as compared to sinus rhythm atrial myocardium.Alterations in active and passive tension generation at the sarcomere level, explained by translational and post-translational changes of multiple myofilament proteins, are part of the contractile dysfunction of human cAF and may contribute to the self-perpetuation of the arrhythmia and the development of atrial dilatation.
Actions of hepatocyte growth factor as a local modulator in the kidney: Potential role in pathogenesis of renal disease
Authors: Yoshikage Yo, Ryuichi Morishita, Kei Yamamoto, Naruya Tomita, Iwao Kida, Shin-ichiro Hayashi, Atsushi Moriguchi, Shin-ichiro Kato, Kunio Matsumoto, Toshikazu Nakamura, Jitsuo Higaki, Toshio Ogihara
Journal: Kidney International (1998)
Comparative Morphologic, Histochemical, and Serologic Studies on the Pathogenesis of Casein-Induced and Reticulosarcoma-Induced Amyloidosis in Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: H. E. Christensen, R. Rask-Nielsen
Journal: JNCI Journal of the National Cancer Institute (1962)

To detect possible differences in the pathogenesis of amyloid development induced by casein injections and by the growth of a transplantable reticulo-sarcoma, we conducted morphologic and histochemical investigations on organs and electrophoretic investigations on serums from casein-treated and sarcoma-bearing mice killed at various intervals during the induction period. The morphologic examinations followed the amyloid development from a phase with proliferative, pyroninophilic reticular cells through a short inversion stage with cytoplasmic periodic acid-Schiff (PAS) positivity, into the amyloid phase proper with increasing amounts of PAS-positive amyloid deposits. Particular attention was paid to the early stages of amyloid formation. With several histochemical methods, the main finding was that the acid mucopolysaccharides in the amyloid deposits increase during aging of the amyloid substance. Paper electrophoretic examination of serums showed that progressive amyloid development is associated with hypergammaglobulinemia, and is later combined with an increase in the ß- and α2-fractions. In Immunoelectrophoresis these changes manifested themselves as an increase in γ, β3-II (β2A), β3-I, β2-III, β2-I (transferrin), α2-I, and α2-II. The electrophoretic findings were correlated with the concomitant stages of morphologic changes. None of these investigations revealed any fundamental differences among the morphologic, histochemical, and serologic changes observed in the two types of amyloid induction.
Guidelines of care for the management of primary cutaneous melanoma
Authors: Christopher K. Bichakjian, Allan C. Halpern, Timothy M. Johnson, Antoinette Foote Hood, James M. Grichnik, Susan M. Swetter, Hensin Tsao, Victoria Holloway Barbosa, Tsu-Yi Chuang, Madeleine Duvic, Vincent C. Ho, Arthur J. Sober, Karl R. Beutner, Reva Bhushan, Wendy Smith Begolka
Journal: Journal of the American Academy of Dermatology (2011)
Transesophageal Ultrasound Imaging During Stent Implantation to Relieve Superior Vena Cava–to–Intra-atrial Baffle Obstruction After Mustard Repair of Transposition of the Great Arteries
Authors: Shuping Ge, Takahiro Shiota, Mary J. Rice, William M. Hellenbrand, David J. Sahn
Journal: Circulation (1995)
Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses.
Authors: N Bhardwaj, J W Young, A J Nisanian, J Baggers, R M Steinman
Journal: The Journal of Experimental Medicine (1993)

Dendritic cells are potent antigen-presenting cells for several primary immune responses and therefore provide an opportunity for evaluating the amounts of cell-associated antigens that are required for inducing T cell-mediated immunity. Because dendritic cells express very high levels of major histocompatibility complex (MHC) class II products, it has been assumed that high levels of ligands bound to MHC products ("signal one") are needed to stimulate quiescent T cells. Here we describe quantitative aspects underlying the stimulation of human blood T cells by a bacterial superantigen, staphylococcal enterotoxin A (SEA). The advantages of superantigens for quantitative studies of signal one are that these ligands: (a) engage MHC class II and the T cell receptor but do not require processing; (b) are efficiently presented to large numbers of quiescent T cells; and (c) can be pulsed onto dendritic cells before their application to T cells. Thus one can relate amounts of dendritic cell-associated SEA to subsequent lymphocyte stimulation. Using radioiodinated SEA, we noted that dendritic cells can bind 30-200 times more superantigen than B cells and monocytes. Nevertheless, this high SEA binding does not underlie the strong potency of dendritic cells to present antigen to T cells. Dendritic cells can sensitize quiescent T cells, isolated using monoclonals to appropriate CD45R epitopes, after a pulse of SEA that occupies a maximum of 0.1% of surface MHC class II molecules. This corresponds to an average of 2,000 molecules per dendritic cell. At these low doses of bound SEA, monoclonal antibodies to CD3, CD4, and CD28 almost completely block T cell proliferation. In addition to suggesting new roles for MHC class II on dendritic cells, especially the capture and retention of ligands at low external concentrations, the data reveal that primary T cells can generate a response to exceptionally low levels of signal one as long as these are delivered on dendritic cells.
Polymorphism of Glutathione S-Transferase M1 and Lung Cancer Risk Among African-Americans and Caucasians in Los Angeles County, California
Authors: S. J. London, A. K. Daly, J. Cooper, W. C. Navidi, C. L. Carpenter, J. R. Idle
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : Glutathione S-transferase Ml (GSTM1) is active in the detoxica-tion of a number of carcinogens, including polyaromatic hydrocarbons, such as those present in cigarette smoke. In about 30%-55% of individuals, depending on the ethnic group, there is a virtual absence of GSTM1 enzyme activity due to deletion of both copies of the GSTM1 gene (GSTM1 null genotype). This genetic polymorphism of the GSTM1 gene locus has been proposed as a risk factor for lung cancer. However, results across studies are inconsistent. Purpose : We conducted a case-control study of patients with incident lung cancer and population control subjects to examine the association between homozygous deletion of the GSTM1 gene and lung cancer risk among African-Americans and Caucasians. Methods : At 35 hospitals in Los Angeles County, California, we identified patients with a first diagnosis of lung cancer between September 1, 1990, and January 6, 1994. Of the 859 potentially eligible case patients, 207 had died by the time their physicians had received our request for permission to contact them. We enrolled 356 eligible case patients (167 African-Americans and 189 Caucasians) and 731 eligible control subjects (258 African-Americans and 473 Caucasians, all residents of Los Angeles County). Samples of white blood cell DNA sufficient for determination of the GSTM1 genotype by a polymerase chain reaction-based assay were obtained from 342 case patients and 716 control subjects. The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homo-zygous deletion of the GSTM1 gene, in total and after stratification by a number of relevant characteristics, were estimated by logistic regression analysis. Results : For patients with all lung cancers combined, the GSTM1 null genotype was associated with an OR of 1.29 (95% CI = 0.94–1.77). The OR was similar among African-Americans (OR = 1.20; 95% CI = 0.72–2.00) and Caucasians (OR = 1.37; 95% CI = 0.91–2.06). The association was strongest for squamous cell carcinoma (OR = 1.57; 95% CI = 0.93–2.63). We observed an OR of 1.77 (95% CI = 1.11–2.82) for the GSTM1 null genotype in relation to lung cancer risk among smokers of less than 40 pack-years, but no association among heavier smokers (OR = 0.90; 95% CI = 0.56–1.44). Conclusions: Our data do not support a substantial association between homozygous deletion of the GSTM1 gene and the risk of lung cancer overall in this population. However, our data do suggest an elevated risk for lighter smokers with this genotype. Implications : Because the power of our analyses within strata of lifetime smoking history was limited, larger studies will be needed to confirm these findings. [J Natl Cancer Inst 87: 1246–1253, 1995]
Induction of interleukin 6 and interleukin 8 expression by Broncho-Vaxom (OM-85 BV) via C-Fos/serum responsive element.
Authors: R. Keul, M. Roth, E. Papakonstantinou, M. Nauck, A. P. Perruchoud, L. H. Block
Journal: Thorax (1996)

Broncho-Vaxom (OM-85 BV) increases the resistance of the respiratory tract to bacterial infections by modulating host immune responses. The compound increases serum IgG levels but decreases IgE levels in patients suffering from chronic bronchitis or chronic obstructive pulmonary disease. It increases concentrations of gamma-interferon (IFN-gamma), IgA, and interleukin (IL)-2 in bronchoalveolar lavage fluid of patients with bronchitis. Treatment with OM-85 BV increases the number of T helper and natural killer cells. In this study the effects of OM-85 BV on transcription of cytokines is investigated in human lung fibroblasts.Transcription and synthesis of IL-6 and IL-8 were assessed in cultured primary human lung fibroblasts using standard methods of Northern blot analysis for the level of mRNAs and enzyme linked immunosorbent assay for proteins.Broncho-Vaxom (OM-85 BV) at different concentrations induced transcription of IL-6 and IL-8. The effect of the drug on transcription of IL-6 and IL-8 genes correlated with secretion of the proteins into cell supernatants. OM-85 BV-dependent expression of the interleukin genes involved C-Fos/serum responsive element (C-Fos/SRE).The data suggest that the various immunopharmacological activities of OM-85 BV that have been described in clinical studies may be explained by its ability to induce expression of IL-6 and IL-8.
CD103 spurs on suppressors
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

An integrin expressed by gut dendritic cells (DCs) gives regulatory T (T reg) cells the green light for suppression, according to a study on page 1051. Annacker and colleagues show that DCs expressing the integrin CD103 are required for T reg cells to subdue gut-attacking effector T cells in a mouse model of inflammatory bowel disease (IBD).Naturally occurring T reg cells help protect against autoimmunity and excessive inflammation by suppressing the activity of effector T cells. This group had previously shown that transferring T reg cells protects against T cell–induced IBD in mice. The suppression of IBD requires the cytokine TGF-β and possibly the high levels of CD103 that are seen in a subset of T reg cells.






Figure 

IBD in mice (right) is suppressed by T reg cells only if dendritic cells express CD103.




Annacker et al. now show, however, that CD103 is not required on the effector T cells for them to induce disease, nor on the T reg cells for them to suppress disease. However, CD103 was not completely expendable. T reg cells could not suppress colitis when transferred into CD103-deficient mice, suggesting that CD103 expression on non–T cells somehow spurs the T reg cells into action.

The relevant CD103-expressing cells were DCs, consistent with the study by Johansson-Lindbom et al. (page 1063) showing that CD103 marks lymph node DCs that originated in the gut. But how these DCs communicate with T reg cells is not clear. Both groups showed that CD103+ DCs, but not CD103− DCs, induced the expression of the gut-homing chemokine receptor CCR9 on effector T cells in vitro. This suggests that CD103+ DCs might similarly induce CCR9 expression on T reg cells, thus endowing them with the ability to migrate to the gut—a possibility not yet tested in vivo.

But the effect of CD103 could also be indirect, suggests senior author Fiona Powrie. CD103 may help trap DCs in the gut by binding to its receptor (E-cadherin) on intestinal epithelial cells, consistent with the recent finding that CD103 is needed to retain pathogenic CD8+ T cells in the gut during graft versus host disease. Although this mechanism remains speculative, retention of DCs in the gut might be a prerequisite for endowing T reg cells with the ability to suppress.
Stratified Meta-Analysis of Intermittent Pneumatic Compression of the Lower Limbs to Prevent Venous Thromboembolism in Hospitalized Patients
Authors: Kwok M. Ho, Jen Aik Tan
Journal: Circulation (2013)

Background— Optimal thromboprophylaxis for patients at risk of bleeding remains uncertain. This meta-analysis assessed whether intermittent pneumatic compression (IPC) of the lower limbs was effective in reducing venous thromboembolism and whether combining pharmacological thromboprophylaxis with IPC would enhance its effectiveness. Methods and Results— Two reviewers searched MEDLINE, EMBASE, and the Cochrane controlled trial register (1966—February 2013) for randomized, controlled trials and assessed the outcomes and quality of the trials independently. Trials comparing IPC with pharmacological thromboprophylaxis, thromboembolic deterrent stockings, no prophylaxis, and a combination of IPC and pharmacological thromboprophylaxis were considered. Trials that used IPC &lt;24 hours or compared different types of IPC were excluded. A total of 16 164 hospitalized patients from 70 trials met the inclusion criteria and were subjected to meta-analysis. IPC was more effective than no IPC prophylaxis in reducing deep vein thrombosis (7.3% versus 16.7%; absolute risk reduction, 9.4%; 95% confidence interval [CI], 7.9–10.9; relative risk, 0.43; 95% CI, 0.36–0.52; P &lt;0.01; I 2 =34%) and pulmonary embolism (1.2% versus 2.8%; absolute risk reduction, 1.6%; 95% CI, 0.9–2.3; relative risk, 0.48; 95% CI, 0.33–0.69; P &lt;0.01; I 2 =0%). IPC was also more effective than thromboembolic deterrent stockings in reducing deep vein thrombosis and appeared to be as effective as pharmacological thromboprophylaxis but with a reduced risk of bleeding (relative risk, 0.41; 95% CI, 0.25–0.65; P &lt;0.01; I 2 =0%). Adding pharmacological thromboprophylaxis to IPC further reduced the risk of deep vein thrombosis (relative risk, 0.54; 95% CI, 0.32–0.91; P =0.02; I 2 =0%) compared with IPC alone. Conclusions— IPC was effective in reducing venous thromboembolism, and combining pharmacological thromboprophylaxis with IPC was more effective than using IPC alone.
TV: Horizon---Homeopathy: The Test
Authors: T. Jackson
Journal: BMJ (2002)

Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> BBC 2, 26 November at 9 pm Medicine can be a bit like magic. Who better then to employ to investigate research results that make no scientific sense than a magician? In 1988 Sir John Maddox, the then editor of the scientific journal Nature , did just that. Nature had published a paper by a celebrated French scientist, Jacques Benveniste, in which Benveniste claimed to have found the evidence that made homoeopathy scientifically credible. As a condition for publishing the paper, Nature insisted it be allowed to take a team of investigators to inspect Benveniste's laboratory. One of the people that Maddox took … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
SPECIFIC COAGULASES OF STAPHYLOCOCCUS AUREUS
Authors: Charles H. Rammelkamp, Margaret M. Hezebicks, John H. Dingle
Journal: The Journal of Experimental Medicine (1950)

Three staphylococcal coagulases termed I, II, and III were differentiated by measuring the antibody titer of human sera. Coagulases I and II are antigenically distinct; coagulase III appears to be related to both coagulases I and II. These results were confirmed by specific neutralization experiments. These observations emphasize the importance of employing the correct type of coagulase in studying the role of this substance in the pathogenesis of staphylococcal infections. Preliminary observations in animals indicate that specific anticoagulase develops following induced infections. The role of this antibody in the recovery mechanism remains to be determined.
Aberrant recombination and the origin of Klinefelter syndrome
Authors: N.S. Thomas
Journal: Human Reproduction Update (2003)

Trisomy is the most commonly identified chromosome abnormality in humans, occurring in at least 4% of all clinically recognized pregnancies; it is the leading known cause of pregnancy loss and of mental retardation. Over the past decade, molecular studies have demonstrated that most human trisomies originate from errors at maternal meiosis I. However, Klinefelter syndrome is a notable exception, as nearly one‐half of all cases derive from paternal non‐disjunction. In this review, the data on the origin of sex chromosome trisomies are summarized, focusing on the 47,XXY condition. Additionally, the results of recent genetic mapping studies are reviewed that have led to the identification of the first molecular correlate of autosomal and sex chromosome non‐disjunction; i.e. altered levels and positioning of meiotic recombinational events.
Cellular Telephones and Cancer--a Nationwide Cohort Study in Denmark
Authors: C. Johansen, J. D. Boice, J. K. McLaughlin, J. H. Olsen
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Use of cellular telephones is increasing exponentially and has become part of everyday life. Concerns about possible carcinogenic effects of radiofrequency signals have been raised, although they are based on limited scientific evidence. Methods: A retrospective cohort study of cancer incidence was conducted in Denmark of all users of cellular telephones during the period from 1982 through 1995. Subscriber lists from the two Danish operating companies identified 420 095 cellular telephone users. Cancer incidence was determined by linkage with the Danish Cancer Registry. All statistical tests are two-sided. Results: Overall, 3391 cancers were observed with 3825 expected, yielding a significantly decreased standardized incidence ratio (SIR) of 0.89 (95% confidence interval [CI] = 0.86 to 0.92). A substantial proportion of this decreased risk was attributed to deficits of lung cancer and other smoking-related cancers. No excesses were observed for cancers of the brain or nervous system (SIR = 0.95; 95% CI = 0.81 to 1.12) or of the salivary gland (SIR = 0.72; 95% CI = 0.29 to 1.49) or for leukemia (SIR = 0.97; 95% CI = 0.78–1.21), cancers of a priori interest. Risk for these cancers also did not vary by duration of cellular telephone use, time since first subscription, age at first subscription, or type of cellular telephone (analogue or digital). Analysis of brain and nervous system tumors showed no statistically significant SIRs for any subtype or anatomic location. Conclusions: The results of this investigation, the first nationwide cancer incidence study of cellular phone users, do not support the hypothesis of an association between use of these telephones and tumors of the brain or salivary gland, leukemia, or other cancers.
Endoscopic Ultrasound (Eus)-Guided Placement of Fiducial Markers for Image-Guided Radiation Therapy in Patients with Pancreatic or Hepatic Malignancies
Authors: Tae Jun Song, Sang Soo Lee, Do Hyun Park, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim
Journal: Annals of Oncology (2013)
Sleep for Preserving and Transforming Episodic Memory
Authors: Marion Inostroza, Jan Born
Journal: Annual Review of Neuroscience (2013)

Sleep is known to support memory consolidation. Here we review evidence for an active system consolidation occurring during sleep. At the beginning of this process is sleep's ability to preserve episodic experiences preferentially encoded in hippocampal networks. Repeated neuronal reactivation of these representations during slow-wave sleep transforms episodic representations into long-term memories, redistributes them toward extrahippocampal networks, and qualitatively changes them to decontextualized schema-like representations. Electroencephalographic (EEG) oscillations regulate the underlying communication: Hippocampal sharp-wave ripples coalescing with thalamic spindles mediate the bottom-up transfer of reactivated memory information to extrahippocampal regions. Neocortical slow oscillations exert a supraordinate top-down control to synchronize hippocampal reactivations of specific memories to their excitable up-phase, thus allowing plastic changes in extrahippocampal regions. We propose that reactivations during sleep are a general mechanism underlying the abstraction of temporally stable invariants from a flow of input that is solely structured in time, thus representing a basic mechanism of memory formation.
Sarcoplasmic reticulum-associated cyclic adenosine 5'-monophosphate phosphodiesterase activity in normal and failing human hearts.
Authors: M A Movsesian, C J Smith, J Krall, M R Bristow, V C Manganiello
Journal: Journal of Clinical Investigation (1991)

Sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was examined in microsomes prepared from the left ventricular myocardium of eight heart transplant recipients with end-stage idiopathic dilated cardiomyopathy and six unmatched organ donors with normal cardiac function. At cAMP concentrations less than or equal to 1.0 microM, sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was functionally homogeneous. cAMP phosphodiesterase activity was inhibited competitively by cGMP (Ki = 0.031 +/- 0.008 microM) and the cilostamide derivative OPC 3911 (Ki = 0.018 +/- 0.004 microM), but was essentially insensitive to rolipram. Vmax and Km were 781.7 +/- 109.2 nmol/mg per min and 0.188 +/- 0.031 microM, respectively, in microsomes prepared from nonfailing hearts and 793.9 +/- 68.9 nmol/mg per min and 0.150 +/- 0.027 microM in microsomes prepared from failing hearts. Microsomes prepared from nonfailing and failing hearts did not differ with respect to either the ratio of cAMP phosphodiesterase activity to ATP-dependent Ca2+ accumulation activity or the sensitivity of cAMP phosphodiesterase activity to inhibition by OPC 3911. These data suggest that the diminished inotropic efficacy of phosphodiesterase inhibitors in failing human hearts does not result from changes in the level, kinetic properties, or pharmacologic sensitivity of sarcoplasmic reticulum-associated cAMP phosphodiesterase activity.