tbuckley/cabot-search huggingface dataset:
Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association
Authors: W. R. Wilson
Journal: JAMA (1995)

<h3>Objective.</h3> —To provide guidelines for the treatment of endocarditis in adults caused by the following microorganisms: viridans streptococci and other streptococci, enterococci, staphylococci, and fastidious gram-negative bacilli of the HACEK group. <h3>Participants.</h3> —An ad hoc writing group appointed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young. <h3>Evidence.</h3> —Published studies of the treatment of patients with endocarditis and the collective clinical experience of this group of experts. <h3>Consensus Process.</h3> —The recommendations were formulated during meetings of the working group and were prepared by a writing committee after the group had agreed on the specific therapeutic regimens. The consensus statement was subsequently reviewed by standing committees of the American Heart Association and by a group of experts not affiliated with the working group. <h3>Conclusions.</h3> —Sufficient evidence has been published that recommendations regarding treatment of the most common microbiological causes of endocarditis (viridans streptococci, enterococci,<i>Streptococcus bovis</i>, staphylococci, and the HACEK organisms) are justified. There are insufficient published data to make a strong statement regarding the efficacy of specific therapeutic regimens for cases of endocarditis due to microorganisms that uncommonly cause endocarditis. As a useful aid to the practicing clinician, the writing group developed a consensus opinion regarding management of endocarditis caused by the most commonly encountered microorganisms and regarding those cases due to infrequent causes of endocarditis. (<i>JAMA</i>. 1995;274:1706-1713)
Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease.
Authors: A Mizoguchi, E Mizoguchi, C Chiba, G M Spiekermann, S Tonegawa, C Nagler-Anderson, A K Bhan
Journal: The Journal of Experimental Medicine (1996)

Spontaneous inflammatory bowel disease (IBD) resembling human ulcerative colitis develops in mice mutant for the T cell receptor alpha gene (TCR-alpha-/-). TCR-alpha-/- mice lack TCR-alpha/beta+ cells but contain TCR-gamma/delta+ cells and a small population of a unique CD4+, TCR-alpha-/beta+(low) cells. Since all the immunoglobulin (Ig) classes are present in these mice, help to B cells must be provided by cells other than TCR-alpha/beta+ cells. In the present study, we found serum levels of IgG1 and IgG2 to be markedly increased in TCR-alpha-/- mice with IBD as compared to TCR-alpha-/- mice without IBD or TCR-alpha+/- controls. An increase in IgG1-, IgG2a- and IgA- but not IgM-secreting mesenteric lymph node (MLN) B cells was detected in TCR-alpha-/- mutant mice. There was also a marked increase in MLN B cells secreting autoantibody (IgG) to tropomyosin, a cytoskeletal protein. Examination of the hyperplastic MLN showed a marked increase in the number of B, TCR-delta+, and CD4+ TCR-alpha-/beta+ cells, similar to the cell population observed at the site of colonic inflammation. Analysis of spontaneous cytokine production by MLN cells using an enzyme-linked immunospot assay, immunohistochemistry, and reverse transcription/polymerase chain reaction showed a decrease of interleukin 2 (IL-2) but a marked increase of IL-4 and interferon gamma (IFN-gamma) production in TCR-alpha-/- mice with IBD as compared to TCR-alpha-/- mice without IBD and TCR alpha+/- control mice. Both TCR-alpha-/beta+ and TCR-delta+ cells were found to be capable of producing IL-4; IFN-gamma was produced mostly by non-T cells, many of which were shown to be CD3- NK 1.1+ cells. We propose that the cytokine imbalance present in these mice results in expansion of B cells, production and switching of autoantibodies to IgG2 subclass, and development of IBD. It is possible that the unusual CD4+ TCR-alpha-/beta+ population and expanded TCR-gamma/delta+ population present in TCR-alpha-/- mice plays a central role in this abnormal immune response.
Response to Sinkkonen: Ultraviolet reflectance in autumn leaves and the un-naming of colours
Authors: Marco Archetti, Thomas F. Döring, Snorre B. Hagen, Nicole M. Hughes, Simon R. Leather, David W. Lee, Simcha Lev-Yadun, Yiannis Manetas, Helen J. Ougham, Paul G. Schaberg
Journal: Trends in Ecology & Evolution (2009)
Assessment of prognostic scores in brain metastases from breast cancer
Authors: Emeline Tabouret, Philippe Metellus, Anthony Gonçalves, Benjamin Esterni, Emmanuelle Charaffe-Jauffret, Patrice Viens, Agnés Tallet
Journal: Neuro-Oncology (2013)

Breast cancer (BC) is the second most common cause of brain metastases (BM). Optimal management of BM from BC is still debated. In an attempt to provide appropriate treatment and to assist with optimal patient selection, several specific prognostic classifications for BM from BC have been established. We evaluated the prognostic value and validity of the 6 proposed scoring systems in an independent population of BC patients with BM.We retrospectively reviewed all consecutive BC patients referred to our institution for newly diagnosed BM between October 1995 and July 2011 (n = 149). Each of the 6 scores proposed for BM from BC (Sperduto, Niwinska, Park, Nieder, Le Scodan, and Claude) was applied to this population. The discriminative ability of each score was assessed using the Brier score and the C-index. Individual prognostic values of clinical and histological factors were analyzed using uni- and multivariate analyses.Median overall survival was 15.1 months (95% CI,11.5-18.7). Sperduto-GPA (P < .001), Nieder (P < .001), Park (P < .001), Claude (P < .001), Niwinska (P < .001), and Le Scodan (P = .034) scores all showed significant prognostic value. The Nieder score showed the best discriminative ability (C-index, 0.672; Brier score error reduction, 16.1%).The majority of prognostic scores were relevant for patients with BM from BC in our independent population, and the Nieder score seems to present the best predictive value but showed a relatively low positive predictive value. Thus, these results remain insufficient and challenge the routine use of these scoring systems.
A Coordinated Change in Chemokine Responsiveness Guides Plasma Cell Movements
Authors: Diana C. Hargreaves, Paul L. Hyman, Theresa T. Lu, Vu N. Ngo, Afshin Bidgol, Gen Suzuki, Yong-Rui Zou, Dan R. Littman, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2001)

Antibody-secreting plasma cells are nonrecirculatory and lodge in splenic red pulp, lymph node medullary cords, and bone marrow. The factors that regulate plasma cell localization are poorly defined. Here we demonstrate that, compared with their B cell precursors, plasma cells exhibit increased chemotactic sensitivity to the CXCR4 ligand CXCL12. At the same time, they downregulate CXCR5 and CCR7 and have reduced responsiveness to the B and T zone chemokines CXCL13, CCL19, and CCL21. We demonstrate that CXCL12 is expressed within splenic red pulp and lymph node medullary cords as well as in bone marrow. In chimeric mice reconstituted with CXCR4-deficient fetal liver cells, plasma cells are mislocalized in the spleen, found in elevated numbers in blood, and fail to accumulate normally in the bone marrow. Our findings indicate that as B cells differentiate into plasma cells they undergo a coordinated change in chemokine responsiveness that regulates their movements in secondary lymphoid organs and promotes lodgment within the bone marrow.
PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice
Authors: José Iglesias, Sebastian Barg, David Vallois, Shawon Lahiri, Catherine Roger, Akadiri Yessoufou, Sylvain Pradevand, Angela McDonald, Claire Bonal, Frank Reimann, Fiona Gribble, Marie-Bernard Debril, Daniel Metzger, Pierre Chambon, Pedro Herrera, Guy A. Rutter, Marc Prentki, Bernard Thorens, Walter Wahli
Journal: Journal of Clinical Investigation (2012)

PPARβ/δ protects against obesity by reducing dyslipidemia and insulin resistance via effects in muscle, adipose tissue, and liver. However, its function in pancreas remains ill defined. To gain insight into its hypothesized role in β cell function, we specifically deleted Pparb/d in the epithelial compartment of the mouse pancreas. Mutant animals presented increased numbers of islets and, more importantly, enhanced insulin secretion, causing hyperinsulinemia. Gene expression profiling of pancreatic β cells indicated a broad repressive function of PPARβ/δ affecting the vesicular and granular compartment as well as the actin cytoskeleton. Analyses of insulin release from isolated PPARβ/δ-deficient islets revealed an accelerated second phase of glucose-stimulated insulin secretion. These effects in PPARβ/δ-deficient islets correlated with increased filamentous actin (F-actin) disassembly and an elevation in protein kinase D activity that altered Golgi organization. Taken together, these results provide evidence for a repressive role for PPARβ/δ in β cell mass and insulin exocytosis, and shed a new light on PPARβ/δ metabolic action.
Long-term exposures to air pollution
Authors: J. G Ayres
Journal: Thorax (2007)

Methodological problems of retrospective studies

In the 1980s the comfortable belief that air pollution was no longer a public health issue was shaken by the appearance of the Six Cities study from the USA which revealed dose-related health effects (ranging from symptoms to mortality) at levels of air pollutants at that time considered to be safe.1 Since then there has been a dramatic rise in the number of publications on air pollution from all parts of the world which have resulted in two broad outcomes: a far better understanding of the mechanisms by which ostensibly “low” concentrations of pollutants impact on the lung and increasing awareness within governments of the need to tighten air quality standards. Most epidemiological studies over this time have considered the effects of day-to-day changes in air pollution on daily events such as deaths and hospital admissions (so-called time-series studies).2 While these studies are in theory easy to undertake, being based on routinely collected data, they usually lack individual information other than cause of death or admission, age and gender. Using this information, in 1998 the UK’s Committee on Medical Effects of Air Pollutants (COMEAP) quantified the health impact of air pollution3 as a stepping stone towards determining the cost effectiveness of further pollution control measures. However, at that time they were unable to quantify the impact of long-term exposures—which even then were thought likely to be far greater than the day-to-day effects—for lack of …
Ablative Allogeneic Hematopoietic Cell Transplantation in Adults 60 Years of Age and Older
Authors: Herschel Wallen, Theodore A. Gooley, H. Joachim Deeg, John M. Pagel, Oliver W. Press, Frederick R. Appelbaum, Rainer Storb, Ajay K. Gopal
Journal: Journal of Clinical Oncology (2005)

To evaluate outcomes of ablative allogeneic hematopoietic cell transplantation (HCT) in older patients with hematologic malignancies.We treated 52 patients from 1979 to 2002 with a median age of 62.8 years (range, 60.1 to 67.8 years) using ablative preparative regimens followed by allogeneic HCT from sibling donors. Diagnoses included myelodysplastic syndrome (MDS; n = 35), chronic myeloid leukemia (CML; n = 8), acute myeloid leukemia (AML; n = 6), and other (n = 3). Conditioning regimens included cyclophosphamide (CY) and busulfan (BU) (67%), total-body irradiation and CY (21%), BU-fludarabine (10%), and CY (2%).Eighteen (35%) of 52 patients are alive at a median of 4.6 years (range, 0.8 to 9.1 years) after transplantation. Median overall survival (OS) and progression-free survival were 300 and 218 days, respectively. Three-year OS and relapse rates are estimated to be 34% and 24%, respectively. Nonrelapse mortality (NRM) rates at 100 days and 3 years are estimated to be 27% and 43%, respectively. Grade 3 to 4 acute graft-versus-host disease (GVHD) occurred in 20% of patients, and chronic extensive GVHD was described in 53% of patients. Fourteen (40%) of 35 patients with MDS are alive at a median of 2.8 years (range, 0.8 to 8.2 years). Four of six patients with CML in chronic or accelerated phase are alive at a median of 6.9 years (range, 4.1 to 9.1 years) after transplantation. None of the patients with AML, CML in blast crisis, or other diagnoses have survived. Patients who underwent transplantation after 1993 had improved survival.These data suggest that allogeneic HCT is feasible in selected patients > or = 60 years of age, although novel methods to reduce NRM while maintaining efficacy are needed.
The Effect of Continuous-flow Ventricle Assist Device and Support Time on Pulmonary Artery Pressure in Bridge to Heart Transplant Patients
Authors: Özlem Balcıoğlu, Tahir Yağdı, Çağatay Engin, Sanem Nalbantgil, Serkan Ertugay, Mehdi Zoghi, Sinan Erkul, Bora Baysal, Mustafa Özbaran
Journal: Journal of the American College of Cardiology (2013)
Should Nonalcoholic Fatty Liver Disease Be Included in the Definition of Metabolic Syndrome?
Authors: Giovanni Musso, Roberto Gambino, Simona Bo, Barbara Uberti, Giampaolo Biroli, Gianfranco Pagano, Maurizio Cassader
Journal: Diabetes Care (2008)

The ability of the Adult Treatment Panel III (ATP III) criteria of metabolic syndrome to identify insulin-resistant subjects at increased cardiovascular risk is suboptimal, especially in the absence of obesity and diabetes. Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and is emerging as an independent cardiovascular risk factor. We compared the strength of the associations of ATP III criteria and of NAFLD to insulin resistance, oxidative stress, and endothelial dysfunction in nonobese nondiabetic subjects.Homeostasis model assessment of insulin resistance (HOMA-IR) >2, oxidative stress (nitrotyrosine), soluble adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin), and circulating adipokines (tumor necrosis factor-alpha, leptin, adiponectin, and resistin) were cross-sectionally correlated to ATP III criteria and to NAFLD in 197 unselected nonobese nondiabetic subjects.NAFLD more accurately predicted insulin resistance than ATP III criteria: sensitivity 73 vs. 38% (P = 0.0001); positive predictive value: 81 vs. 62% (P = 0.035); negative predictive value 87 vs. 74% (P = 0.012); positive likelihood ratio 4.39 vs. 1.64 (P = 0.0001); and negative likelihood ratio 0.14 vs. 0.35 (P = 0.0001). Adding NAFLD to ATP III criteria significantly improved their diagnostic accuracy for insulin resistance. Furthermore, NAFLD independently predicted HOMA-IR, nitrotyrosine, and soluble adhesion molecules on logistic regression analysis; the presence of NAFLD entailed more severe oxidative stress and endothelial dysfunction, independent of adiposity or any feature of the metabolic syndrome in insulin-resistant subjects.NAFLD is more tightly associated with insulin resistance and with markers of oxidative stress and endothelial dysfunction than with ATP III criteria in nonobese nondiabetic subjects and may help identify individuals with increased cardiometabolic risk in this population.
Hepatitis C virus antibodies in haemodialysis patients
Authors: U Schlipköter, M Roggendorf, G Ernst, R Rasshofer, F Deinhardt, A Weise, U Gladziwa, N Luz, Ikuo Tamura, Yasunori Kobayashi, Tetsuzo Koda, Hiroshi Ichimura, Osamu Kurimura, Takahisa Takasugi, Takashi Kurimura, K Yamaguchi, Y Nishimura, N Fukuoka, J Machida, S Ueda, Y Kusumoto, G Futami, T Ishii, K Takatsuki
Journal: The Lancet (1990)
RESTRICTION OF SPECIFICITY IN THE PRECURSORS OF BONE MARROW-ASSOCIATED LYMPHOCYTES
Authors: L. Lafleur, R. G. Miller, R. A. Phillips
Journal: The Journal of Experimental Medicine (1973)

Previous work has shown that the immediate precursor of B lymphocytes (PB cell) has many properties that distinguish it from both B lymphoctes and hemopoietic stem cells. Size, density, tissue distribution, and sensitivity to cytotoxic antisera differ for each type of cell. The work described here was designed to study three aspects of the differentiation of PB cells. First, since PB cells probably have immunoglobulin surface receptors, fluorescein-labeled anti-immunoglobulin antiserum was used in an attempt to investigate directly the physical properties of PB cells. The use of this labeled antiserum revealed a population of cells with properties similar to the PB cells defined by the functional assays. Second, the differentiative potential of PB cells was studied by comparing the size of the total population of PB cells, as determined with fluorescein-labeled anti-immunoglobulin antiserum, to the size of the population of PB cells responding in a functional assay with a specific antigen. The cells responding in the functional assay represent only 0.1% of the total population of PB cells. This observation suggests that PB cells are not pluripotent stem cells of the immune system. Finally, the kinetics of the differentiation of PB cells to B lymphocytes was studied. The differentiation to mature lymphocytes involves at least one intermediate stage in which cells larger than mature B cells are active in a functional assay for B cells. These large B cells are present in irradiated mice soon after transplantation of PB cells, but by 20 days the majority of the B cells are typical small lymphocytes.
Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies
Authors: L. R Dolovich, A. Addis, J M R. Vaillancourt, J D B. Power, G. Koren, T. R Einarson
Journal: BMJ (1998)

ABSTRACT. Several animal studies suggest that T cell–mediated immunodeficiency may play a role in the progression of atherosclerosis. This study examined the association between lymphocyte subsets and atherosclerotic events in renal transplant recipients. A total of 302 consecutive renal transplant recipients were enrolled in this prospective study. Peripheral blood lymphocyte subsets were quantified and analyzed with respect to other known cardiovascular risk factors. The patients were followed for a mean duration of 23.5 ± 4.5 mo. Mean CD4, CD8, and CD19 cell levels were 511 ± 290/mm<sup>3</sup>, 553 ± 596/mm<sup>3</sup>, and 66 ± 62/mm<sup>3</sup>, respectively. CD4 levels were positively related to transplant duration (<i>r</i> = 0.32; <i>P</i> = 0.02) and inversely related to age (<i>r</i> = 0.35; <i>P</i> = 0.01). Twenty-five atherosclerotic events (AE) occurred in 25 patients (8.3%). CD4 levels were lower in patients who experienced CVE (288 ± 170/mm<sup>3</sup><i>versus</i> 531 ± 290/mm<sup>3</sup>; <i>P</i> &lt; 0.0001). Cox regression analysis showed that patients in the three upper quartiles of CD4 cell count had a decreased risk of CVE compared with those in the lowest quartile. There was a linear increase in risk of CVE with decreasing CD4 cell count (<i>P</i> &lt; 0.0001). A CD4 cell count in the highest quartile (&gt;663/mm<sup>3</sup>) divided the risk of CVE by 10 as compared with the lowest quartile. In conclusion, CD4 lymphocytopenia is an independent risk factor for the development of cardiovascular complications in renal transplant recipients, suggesting that impaired immune response promotes accelerated atherogenesis in this population. E-mail: dducloux@chu-besancon.fr
Perception and psychoses: The role of glutamatergic transmission within the nucleus accumbens septi
Authors: Pascual Angel Gargiulo, Adriana Ines Landa de Gargiulo
Journal: Behavioral and Brain Sciences (2004)

In agreement with Behrendt &amp; Young (B&amp;Y), we considered the role of perception disturbances in schizophrenia in our first clinical approaches, using the Bender test with schizophrenic patients. Following this, we reproduced nuclear symptoms of schizophrenia in animal models, showing that perceptual disturbances, acquisition disturbances, and decrease in affective levels can be induced by glutamatergic blockade within the nucleus accumbens septi. Our results link the proposed corticostriatal dysfunction with the thalamocortical disturbances underlying perceptual problems reviewed by B&amp;Y.
The pineal gland and reproduction
Authors: V Aleandri
Journal: Human Reproduction Update (1996)

The hormonal activity of the pineal gland is influenced by both the dark-light cycle and the seasonal cycle, causing it to play an important role in the neuroendocrine control of reproductive physiology. This is especially evident in seasonally breeding animals, in which reproductive function is clearly influenced by seasonal variations in the duration of night and day. Humans are not seasonal breeders. Nevertheless, seasonal fluctuations have been described in human reproduction, and the pineal gland also appears to exert an important role in the neuroendocrine regulation of human reproductive physiology. There is evidence that the epiphysis is involved in the control of sexual maturation. In rats, the maternal pineal appears to influence the gonadal and genital development and function of offspring; this hypothesis has yet to be confirmed in humans. The pineal apparently influences human reproductive function not only at the hypothalamic-pituitary level, by inhibition of the hypothalamic pulsatile secretion of gonadotrophin-releasing hormone, but also at the gonadal level, where melatonin receptors have also been found. In addition, melatonin is reported to increase serum prolactin concentrations in both rats and humans. It has been suggested that melatonin is involved in the control of menstrual cyclicity.
Cardiac Myosin Binding Protein C
Authors: Saul Winegrad
Journal: Circulation Research (1999)

Myosin binding protein C (MyBP-C) is one of a group of myosin binding proteins that are present in the myofibrils of all striated muscle. The protein is found at 43-nm repeats along 7 to 9 transverse lines in a portion of the A band where crossbridges are found (C zone). MyBP-C contains myosin and titin binding sites at the C terminus of the molecule in all 3 of the isoforms (slow skeletal, fast skeletal, and cardiac). The cardiac isoform also includes a series of residues that contain 3 phosphorylatable sites and an additional immunoglobulin module at the N terminus that are not present in skeletal isoforms. The following 2 major functions of MyBP-C have been suggested: (1) a role in the formation of the sarcomeric myofibril as a result of binding to myosin and titin and (2) in the case of the cardiac isoform, regulation of contraction through phosphorylation. The first is supported by the demonstrated effect of MyBP-C on the packing of myosin in the thick filament, the coincidence of appearance of sarcomeres and MyBP-C during myofibrillogenesis, and the defective formation of sarcomeres when the titin and/or myosin binding sites of MyBP-C are missing. The second is supported by the specific phosphorylation sites in cardiac MyBP-C, the presence in the thick filament of an enzyme specific for MyBP-C phosphorylation, the alteration of thick filament structure by MyBP-C phosphorylation, and the accompaniment of MyBP-C phosphorylation with all major physiological mechanisms of modulation of inotropy in the heart.