tbuckley/cabot-search huggingface dataset:
Differences in Direct Effects of Adrenergic Stimuli on Coronary, Cutaneous, and Muscular Vessels
Authors: Allyn L. Mark, Francois M. Abboud, Phillip G. Schmid, Donald D. Heistad, Howard E. Mayer
Journal: Journal of Clinical Investigation (1972)

Direct effects of adrenergic stimuli on coronary vessels in dogs were compared with effects on vessels to skin (hind paw) and skeletal muscle (gracilis muscle) after intravenous administration of practolol (2 mg/kg), a selective myocardial beta receptor blocker which minimized indirect effects of myocardial stimulation on coronary vascular resistance. The left circumflex coronary, cranial tibial, and gracilis arteries were perfused separately but simultaneously at constant flow. Perfusion pressures, left ventricular pressure and dP/dt. and heart rate were recorded. Changes in perfusion pressure to each bed reflected changes in vascular resistance. The direct constrictor effects of sympathetic nerve stimulation, norepinephrine and phenylephrine on coronary vessels were minimal compared with effects on cutaneous and muscular vessels. Subsequent blockade of vascular beta receptors did not augment the constrictor responses. Angiotensin, a nonadrenergic stimulus, produced striking coronary vasoconstriction which exceeded that in skin and approximated that in muscle. These results suggests that there is a paucity of alpha adrenergic receptors in coronary vessels compared to cutaneous and muscular vessels. Direct dilator responses to isoproterenol were similar in coronary and cutaneous vessels, but were greater in muscular vessels. Responses to glyceryl trinitrate, a nonadrenergic dilator, also were greater in skeletal muscle. Therefore, differences in effects of isoproterenol on the three beds may reflect differences in reactivity to dilator stimuli rather than differences in the density of beta receptors. In contrast to norepinephrine, the predominant direct effect of epinephrine on coronary vessels was dilatation mediated through activation of vascular beta receptors. A constrictor effect caused by stimulation of alpha receptors was unmasked by propranolol.Finally, the order of potency of agonists in stimulating coronary vascular beta receptors and the demonstration of selective beta receptor blockade with practolol suggest that beta receptors in coronary vessels resemble those in peripheral vessels more than those in myocardium.
THE TOXOPLASMA GONDII OOCYST FROM CAT FECES
Authors: J. P. Dubey, Nancy L. Miller, J. K. Frenkel
Journal: The Journal of Experimental Medicine (1970)

Coccidian oocysts resembling those of Isospora bigemina were excreted by cats fed Toxoplasma. In order to identify these oocysts with Toxoplasma infectivity a number of critical comparisons were made. The appearance of oocysts and Toxoplasma infectivity was simultaneous in the feces of 23 of 24 adult cats, 3-5 days after feeding of Toxoplasma cysts; in the feces of 4 out of 9 cats, 7-10 days after feeding of trophozoites; and in 8 out of 17 cats, 20-24 days after feeding of cat feces containing oocysts. Oocysts and infectivity were present in similar numbers, and they disappeared simultaneously from the feces of cats. Oocysts and infectivity were also observed simultaneously in the feces of 9 kittens, 1-2 days old, fed Toxoplasma cysts. Oocysts could not be separated from infectivity by filtration, by continuous particle electrophoresis, or by density gradient centrifugation. Excystation of oocysts was followed by an increase in titer of Toxoplasma infectivity. Unsporulated oocysts in fresh cat feces were noninfectious to mice, but oocyst sporulation was associated quantitatively with the development of infectivity at different temperatures and conditions of oxygenation. Maximum oocyst sporulation at 48 hr correlated with the development of maximum Toxoplasma infectivity. 1 and 2% sulfuric acid, and 2.5% potassium dichromate were found to be the best preservatives for sporulation of oocysts and for the development of Toxoplasma infectivity. Low sporulation rates in 0.1% formalin, 20% ethanol, and in water were associated with low infectivity in these reagents. Neither Toxoplasma infectivity nor oocysts developed in 0.3% formalin, 1% ammonium hydroxide, or 1% iodine in 20% ethanol. Oocysts, sporocysts, and sporozoites were stained specifically with Toxoplasma antibody in the indirect fluorescent antibody test. Typical coccidian stages, schizonts, and male and female gametocytes were found in the epithelium of the small intestine of kittens fed Toxoplasma cysts. The classification of T. gondii is discussed in relation to that of other isosporan coccidia of cats and dogs. The term "Toxoplasma oocyst" is introduced and Toxoplasma is classified in the family Toxoplasmidae of the suborder Eimeriina. The species Isospora bigemina is restricted to dogs, and I. cati to cats. I. felis and so-called I. rivolta from cats were noninfectious to dogs, and did not confer immunity to subsequent infection with I. canis and I. rivolta from dogs.
STIM1 Restores Coronary Endothelial Function in Type 1 Diabetic Mice
Authors: Irene A. Estrada, Reshma Donthamsetty, Patryk Debski, Meng-Hua Zhou, Shenyuan L. Zhang, Jason X.-J. Yuan, Wenlong Han, Ayako Makino
Journal: Circulation Research (2012)

The endoplasmic reticulum (ER) is a major intracellular Ca(2+) store in endothelial cells (ECs). The Ca(2+) concentration in the ER greatly contributes to the generation of Ca(2+) signals that regulate endothelial functions. Many proteins, including stromal interaction molecule 1/2 (STIM1/2), Orai1/2/3, and sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 3 (SERCA3), are involved in the ER Ca(2+) refilling after store depletion in ECs.This study is designed to examine the role of Ca(2+) in the ER in coronary endothelial dysfunction in diabetes.Mouse coronary ECs (MCECs) isolated from diabetic mice exhibited (1) a significant decrease in the Ca(2+) mobilization from the ER when the cells were treated by SERCA inhibitor, and (2) significant downregulation of STIM1 and SERCA3 protein expression in comparison to the controls. Overexpression of STIM1 restored (1) the increase in cytosolic Ca(2+) concentration due to Ca(2+) leak from the ER in diabetic MCECs, (2) the Ca(2+) concentration in the ER, and (3) endothelium-dependent relaxation that was attenuated in diabetic coronary arteries.Impaired ER Ca(2+) refilling in diabetic MCECs, due to the decrease in STIM1 protein expression, attenuates endothelium-dependent relaxation in diabetic coronary arteries, while STIM1 overexpression has a beneficial and therapeutic effect on coronary endothelial dysfunction in diabetes.
The Composition of a Primary T Cell Response Is Largely Determined by the Timing of Recruitment of Individual T Cell Clones
Authors: Philippe Bousso, Jean-Pierre Levraud, Philippe Kourilsky, Jean-Pierre Abastado
Journal: The Journal of Experimental Medicine (1999)

Primary T cell responses rely on the recruitment and proliferation of antigen-specific T cell precursors. The extent of expansion of each individual T cell clone may depend on (a) its frequency before immunization, (b) its proliferative capacity, and (c) the time at which it first encounters its cognate antigen. In this report, we have analyzed the relative contribution of each of these parameters to the shaping of immune repertoires in the T cell response specific for the epitope 170-179 derived from HLA-Cw3 and presented by Kd. By means of hemisplenectomy, we compared immune and naive repertoires in the same animal and found that the frequency of all expanded T cell clones was extremely low before immunization. In particular, the most expanded clones did not derive from high-frequency precursors. In addition, recruited T cells were found to proliferate at the same rate, irrespective of their T cell antigen receptor sequence. Finally, we showed that only T cells that encounter the antigen at early time points account for a significant part of the specific response. Therefore, the contribution of a T cell clone to the immune response is mostly determined by the time of its entry into the immune repertoire, i.e., the time of first cell division after antigen encounter.
Absence of NO synthase type II expression in fetal liver from pregnant rats under septic shock conditions
Authors: M Casado, M Velasco, L Bosca, P Martin-Sanz
Journal: Hepatology (1997)

Treatment of rats at 21 days' gestation with lipopolysaccharide (LPS) induced type II NO synthase (iNOS) expression in maternal liver but completely failed to elicit this response in the corresponding fetal tissue. The impaired response of fetal liver cannot be attributed to alterations in the sensitivity of this organ to LPS or to proinflammatory cytokines involved in iNOS expression (tumor necrosis factor α [TNF-α], interferon gamma [IFN-γ]), because cultured fetal and adult hepatocytes similarly responded to these factors. Measurement of TNF-α and IFN-γ levels in maternal and fetal serum showed a restricted permeability of placenta to these cytokines, results that were in agreement with the absence of iNOS expression in fetal liver. Moreover, analysis of nuclear factor kappaB, which is required for iNOS expression, showed an activation in nuclear extracts from livers of mothers under septic shock conditions but not in the corresponding fetal livers. However, cultured fetal hepatocytes prepared from mothers in septic shock displayed an anomalous pattern of iNOS expression, including a decreased response to LPS as well as a shift in sensitivity to TNF-α. These hepatocytes from LPS-treated mothers showed significant expression of iNOS in the absence of added stimuli. These results suggest that there is a priming of the fetal hepatocytes from mothers with septic shock. The characterization of the factors causing this priming process might provide additional clues understanding the control of iNOS expression in liver.
Phylogenetic Evidence for Frequent Positive Selection and Recombination in the Meningococcal Surface Antigen PorB
Authors: Rachel Urwin, Edward C. Holmes, Andrew J. Fox, Jeremy P. Derrick, Martin C. J. Maiden
Journal: Molecular Biology and Evolution (2002)

Previous estimates of rates of synonymous (dS) and nonsynonymous (dN) substitution among Neisseria meningitidis gene sequences suggested that the surface loops of the variable outer membrane protein PorB were under only weak selection pressure from the host immune response. These findings were consistent with studies indicating that PorB variants were not always protective in immunological and microbiological assays and questioned the suitability of this protein as a vaccine component. PorB, which is expressed at high levels on the surface of the meningococcus, has been implicated in mechanisms of pathogenesis and has also been used as a typing target in epidemiological investigations. In this work, using more precise estimates of selection pressures and recombination rates, we have shown that some residues in the surface loops of PorB are under very strong positive selection, as great as that observed in human immunodeficiency virus-1 surface glycoproteins, whereas amino acids within the loops and the membrane-spanning regions of the protein are under purifying selection, presumably because of structural constraints. Congruence tests showed that recombination occurred at a rate that was not sufficient to erase all phylogenetic similarity and did not greatly bias selection analysis. Homology models of PorB structure indicated that many strongly selected sites encoded residues that were predicted to be exposed to host immune responses, implying that this protein is under strong immune selection and requires further examination as a potential vaccine candidate. These data show that phylogenetic inference can be used to complement immunological and biochemical data in the choice of vaccine candidates.
Non-Invasive Visualization of the Cardiac Venous System in Coronary Artery Disease Patients Using 64-Slice Computed Tomography
Authors: Nico R. Van de Veire, Joanne D. Schuijf, Johan De Sutter, Dan Devos, Gabe B. Bleeker, Albert de Roos, Ernst E. van der Wall, Martin J. Schalij, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2006)
Denial of mental illness in athletes
Authors: Timothy D Noakes
Journal: British Journal of Sports Medicine (2000)

<h3>Summary</h3> Fungicides reduce fungal pathogen populations and are essential to food security. Fungicide disturbance of plant microbiomes has received limited attention. Understanding the impacts of fungicides on crop microbiomes in different cropping systems is vital to minimizing unintended consequences while maintaining their use for plant protection. We used amplicon sequencing of fungi and prokaryotes in maize and soybean microbiomes before and after foliar fungicide application in leaves and roots from plots under long-term no-till and conventional tillage managements. We examine fungicide disturbance and microbiome resilience across these treatments. Foliar fungicides directly affected phyllosphere fungal communities, but not root fungal communities or prokaryote communities. Impacts on fungal phyllosphere composition and resiliency were management-dependent and lasted more than thirty days. Fungicides lowered pathogen abundance in maize and soybean and decreased the abundance of Tremellomycetes yeasts, especially the Bulleribacidiaceae, including core microbiome members. Fungicide application reduced network complexity in the soybean phyllosphere. Bulleribacidiaceae often co-occurred with <i>Sphingomonas</i> and <i>Hymenobacter</i> in control plots, but co-occurrences were altered in fungicide plots. Results indicate that foliar fungicides lower pathogen and non-target fungal abundance and may impact prokaryotes indirectly. No-till management was more resilient following fungicide disturbance and recovery.
Drug-Associated Dermatomyositis Following Ipilimumab Therapy
Authors: Shirwa Sheik Ali, Allison L. Goddard, Jason J. Luke, Hilary Donahue, Derrick J. Todd, Andrew Werchniak, Ruth Ann Vleugels
Journal: JAMA Dermatology (2014)

<h3>Importance</h3> Ipilimumab, a human monoclonal antibody targeted against cytotoxic T-lymphocyte antigen 4, has shown promise in the treatment of metastatic melanoma. However, given its mechanism of action, immune-related adverse effects have been reported with this therapy. Despite increasing reports of immune-related adverse effects related to ipilimumab therapy, dermatomyositis associated with this agent has not previously been reported. <h3>Observations</h3> We describe a woman undergoing treatment with ipilimumab for metastatic melanoma who developed classic cutaneous findings of dermatomyositis along with proximal muscle weakness and elevated muscle enzymes. <h3>Conclusions and Relevance</h3> This case adds to the expanding literature regarding immune-related adverse events associated with ipilimumab. To our knowledge, drug-induced dermatomyositis from ipilimumab has not previously been reported. Physicians should be aware of these potential immune-related adverse events and consider drug-associated dermatomyositis in the differential diagnosis in patients receiving ipilimumab who present with a cutaneous eruption or muscle weakness.
A New Culture Model Facilitating Rapid Quantitative Testing of Mitotic Spindle Inhibition in Mammalian Cells2
Authors: M.De Brabander, R. Van de Veire, F. Aerts, S. Geuens, J. Hoebeke
Journal: JNCI Journal of the National Cancer Institute (1976)

A new culture model, which facilitated both mass screening of potential anticancer drugs acting on microtubules and quantitative experiments with known “antitubulins,” was found to have the following advantages: use of mammalian cells (either transformed or not), simplicity of the techniques (phase-contrast microscopy or simple microscopy after Giemsa staining), and ease with which it lent itself to quantification. The model was based on the uniform multimicronucleation response induced by antitubulins in MO cells. The specificity (towards antitubulins) of this response was ascertained by the use of many substances, including most of the known antitubulins and a number of nonrelated cytostatic or cytotoxic compounds. The uniformity of the response was established with the use of time-lapse observation of large numbers of cells and quantitative approaches. The results obtained in this model with the standard antitubulins (colchicine, vinblastine, vincristine) showed similar effects. The major difference between colchicine and the Vinca alkaloids was that colchicine was less reversible, which might be an indication of stronger intracellular binding. The Vinca alkaloids acted synergistically with colchicine when threshold subactive doses were combined, although it is known that they bind at a different site on tubulins. A number of substances that have been claimed or were suspected to interfere with microtubules were tested. The results showed that the following substances were indeed active with MO cells: colchicine, vinblastine, vincristine, podophyllotoxin, rotenone, griseofulvin, mercaptoethanol, benomyl, methyl benzimidazol-2-yl carbamate, and R 17934. Compounds that were inactive on these mammalian cells in culture included isopropyl carbanilate and melatonin, both of which have been shown to be active in other system.
Genetic aspects of atrial fibrillation
Authors: A WIESFELD, M HEMELS, J VANTINTELEN, M VANDENBERG, D VANVELDHUISEN, I VANGELDER
Journal: Cardiovascular Research (2005)

Atrial fibrillation (AF) occurs predominantly in the elderly and is commonly associated with underlying cardiac diseases. A significant number of patients, however, have early onset AF that is not associated with any underlying disease. At present, it is unknown how often this form of AF is familial and how frequently familial AF is due to genetic causes. Recent data suggest that familial AF occurs more frequently than previously recognized. Also, in AF in the setting of underlying diseases, it is suggested that some form of genetic control may be present. Understanding the molecular mechanisms underlying AF may provide insight into the pathogenesis of AF and eventually may lead to improved, patient-tailored rhythm control strategies.
BI-17 * EARLY COGNITIVE FUNCTION TESTS PREDICT EARLY PROGRESSION IN NEWLY-DIAGNOSED GLIOBLASTOMA
Authors: S.-T. Lee, K.-M. Lee, J. W. Kim, M.-J. Park, J.-A. Lim, S.-H. Choi, T. M. Kim, S. H. Lee, S.-H. Park, I.-H. Kim, C.-K. Park
Journal: Neuro-Oncology (2014)

BACKGROUND: Cognitive dysfunction is a characteristic of tumor infiltration and a major morbidity causing functional deterioration in glioblastoma patients. Here we investigated whether pre-operative cognitive function tests can predict early prognosis in glioblastoma. METHODS: Consecutive patients who underwent glioma surgery were evaluated with pre-operative cognitive function tests, including Mini-Mental State Examination, Geriatric Depression Scale, Digit Span Tests (forward and backward), Controlled Oral Ward Association Test, Trail-Making Tests (TMT, type a, b, and c), and Stroop Tests. Pathologically-confirmed glioblastoma were treated with the standard protocol using radiation and temozolomide, and the 6-month progression-free survivals (PFS-6) were analyzed. RESULTS: Among 126 patients who underwent glioma surgery, 55 patients were diagnosed as glioblastoma, and 50 patients were finally eligible for the PFS-6 analysis. Thirty four patients (68%) achieved PFS-6. In the comparison of those without progression (PFS-6) with those with progression (No-PFS-6), there was no difference in the patients' demographics, tumor locations, tumor sizes, performance scores, initial symptoms, and genetic characteristics of tumors. The PFS-6 patients had higher rates of gross total resection, more use of concomitant chemo-radiation, and longer years of total education, than the no-PFS-6 patients. In the cognitive function tests, the PFS-6 patients had better performance in TMT-a, and TMT-b. Other cognitive function tests were not associated with PFS-6. In multivariate logistic regression, TMT-b was the only independent predictor for PFS-6, while age (<50), total education year (>12 yr), gross total resection, concomitant chemo-radiation, and TMT-a were not. Patients with good performance in TMT-b not only showed better early prognosis in the Kaplan-Meier survival analysis, but also had better recursive partitioning analysis classes. CONCLUSION: Our results indicate that the early cognitive function test before surgery can predict the early prognosis in glioblastoma. Poor executive function and slow psychomotor speed as detected in TMT suggest early progression of the tumor.
Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity
Authors: Alice P. Liou, Melissa Paziuk, Jesus-Mario Luevano, Sriram Machineni, Peter J. Turnbaugh, Lee M. Kaplan
Journal: Science Translational Medicine (2013)

Alterations in the gastrointestinal microbiota caused by gastric bypass surgery are sufficient to trigger decreased body weight and adiposity in germ-free mouse recipients.
Prostate-Specific Antigen Screening Trials and Prostate Cancer Deaths: The Androgen Deprivation Connection
Authors: I. E. Haines, G. L. Gabor Miklos
Journal: JNCI Journal of the National Cancer Institute (2013)

Major clinical trials using prostate-specific antigen (PSA) as the screening test to detect localized early-stage prostate cancer and to attempt to change its natural history with early intervention have yielded conflicting interpretations. The US Prostate, Lung, Colorectal, and Ovarian (US PLCO) cancer screening trial concluded that PSA-based screening conferred no meaningful survival benefit, whereas the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the GOTEBORG clinical trial (GOTEBORG) trials claimed statistically significant life-saving benefits. These divergent outcomes have not provided physicians with clarity on the best evidence-based treatment. To determine the extent to which these divergent outcomes are clinically meaningful, we evaluated these data and those of a long-term prospective cohort study in the context of the clinically documented harms of androgen deprivation therapy (ADT). We noted the unheralded fact that in both European trials far more patients received hormonal treatment in the control than the prostatectomy arm, whereas hormonal therapy in the US trial was balanced between arms. We examined this imbalance in ADT treatment and prostate cancer–related deaths in the contexts of contamination, stage migration, and attribution of cause of death, all of which impinge on data interpretation. The ERSPC and GOTEBORG data are compatible with the hypothesis that ADT treatment contributes differentially to an increase in prostate cancer deaths in control patients. If so, the claim of a reduction in prostate cancer deaths in the screened cohort requires reappraisal. The conventional interpretation that PSA screening and radical treatment intervention are the major contributors to the results of these two studies needs more rigorous scientific scrutiny, as does the role of ADT treatment of nonmetastatic disease.