tbuckley/cabot-search huggingface dataset:
A COMPARATIVE STUDY OF THE BIOLOGICAL CHARACTERS AND PATHOGENESIS OF BACILLUS X (STERNBERG), BACILLUS ICTEROIDES (SANARELLI), AND THE HOG-CHOLERA BACILLUS (SALMON AND SMITH)
Authors: Walter Reed, James Carroll
Journal: The Journal of Experimental Medicine (1900)

1. Bacillus X (Sternberg) belongs to the colon group. 2. Bacillus icteroides (Sanarelli) is a member of the hog-cholera group. 3. The various channels of infection, the duration of the disease and the gross and microscopical lesions in mice, guinea-pigs and rabbits are the same for Bacillus icteroides and the hog-cholera bacillus. 4. The clinical symptoms and the lesions observed in dogs inoculated intravenously with Bacillus icteroides, are reproduced in these animals by infection with the hog-cholera bacillus. 5. Bacillus icteroides when fed to the domestic pig causes fatal infection, accompanied by diphtheritic, necrotic and ulcerative lesions in the digestive tract, such as are seen in hogs when infected with the hog-cholera bacillus. 6. This disease may be acquired by exposing swine in pens already infected with Bacillus icteroides, or by feeding them with the viscera of infected pigs. 7. Guinea-pigs may be immunized with sterilized cultures ofBacillus icteroides from a fatal dose of the hog-cholera bacillus and vice versa. 8. Rabbits may be rendered immune by gradually increasing doses of a living culture of Bacillus icteroides of weak virulence from a fatal dose of a virulent culture of the hog-cholera bacillus 9. The sera of animals immunized with Bacillus icteroides and with the hog-cholera bacillus, respectively, show a marked reciprocal agglutinative reaction. 10. While the blood of yellow fever practically does not exercise an agglutinative reaction upon Bacillus icteroides, the blood of hog-cholera agglutinates this bacillus in a much more marked degree, thus pointing, we think, to the closer etiological relationship of this bacillus to hog-cholera than to yellow fever.
A Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin in Patients with Hormone-Refractory Metastatic Prostate Cancer
Authors: Elisabeth I. Heath, David W. Hillman, Ulka Vaishampayan, Shijie Sheng, Fazlul Sarkar, Felicity Harper, Melvin Gaskins, Henry C. Pitot, Winston Tan, S. Percy Ivy, Roberto Pili, Michael A. Carducci, Charles Erlichman, Glenn Liu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with antiproliferative activity in several mouse xenograft models, including prostate cancer models. A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer. Experimental Design: Patients with at least one prior systemic therapy and a rising prostate-specific antigen (PSA) were eligible. Patients received 17-AAG at a dose of 300 mg/m2 i.v. weekly for 3 of 4 weeks. The primary objective was to assess the PSA response. Secondary objectives were to determine overall survival, to assess toxicity, and to measure interleukin-6, interleukin-8, and maspin levels and quality of life. Results: Fifteen eligible patients were enrolled. The median age was 68 years and the median PSA was 261 ng/mL. Patients received 17-AAG for a median number of two cycles. Severe adverse events included grade 3 fatigue (four patients), grade 3 lymphopenia (two patients), and grade 3 back pain (two patients). The median PSA progression-free survival was 1.8 months (95% confidence interval, 1.3-3.4 months). The 6-month overall survival was 71% (95% confidence interval, 52-100%). Conclusions: 17-AAG did not show any activity with regard to PSA response. Due to insufficient PSA response, enrollment was stopped at the end of first stage per study design. The most significant severe toxicity was grade 3 fatigue. Further evaluation of 17-AAG at a dose of 300 mg/m2 i.v. weekly as a single agent in patients with metastatic, hormone-refractory prostate cancer who received at least one prior systemic therapy is not warranted.
Glucocorticoid-Induced Tumor Necrosis Factor Receptor–Related Protein Ligand Subverts Immunosurveillance of Acute Myeloid Leukemia in Humans
Authors: Tina Baessler, Matthias Krusch, Benjamin Joachim Schmiedel, Mercedes Kloss, Katrin Miriam Baltz, Alexander Wacker, Helga Maria Schmetzer, Helmut Rainer Salih
Journal: Cancer Research (2009)

Abstract The reciprocal interaction of tumor cells with the immune system is influenced by various members of the tumor necrosis factor (TNF)/TNF receptor (TNFR) family, and recently, glucocorticoid-induced TNFR-related protein (GITR) was shown to stimulate antitumor immunity in mice. However, GITR may mediate different effects in mice and men and impairs the reactivity of human natural killer (NK) cells. Here, we studied the role of GITR and its ligand (GITRL) in human acute myeloid leukemia (AML). Surface expression of GITRL was observed on AML cells in six of seven investigated cell lines, and 34 of 60 investigated AML patients whereas healthy CD34+ cells did not express GITRL. Furthermore, soluble GITRL (sGITRL) was detectable in AML patient sera in 18 of 55 investigated cases. While the presence of GITRL was not restricted to a specific AML subtype, surface expression was significantly associated with monocytic differentiation. Signaling via GITRL into patient AML cells induced the release of TNF and interleukin-10 (IL-10), and this was blocked by the inhibition of mitogen-activated protein kinases extracellular signal-regulated kinase 1/2. Furthermore, triggering GITR by surface-expressed and sGITRL impaired NK cell cytotoxicity and IFN-γ production in cocultures with leukemia cells, and NK cell reactivity could be restored by blocking GITR and neutralization of sGITRL and IL-10. Thus, whereas a stimulatory role of the GITR-GITRL system in mouse antitumor immunity has been reported, our data show that in humans GITRL expression subverts NK cell immunosurveillance of AML. Our results provide useful information for therapeutic approaches in AML, which, like haploidentical stem cell transplantation, rely on a sufficient NK cell response. [Cancer Res 2009;69(3):1037–45]
Tramiprosate, a drug of potential interest for the treatment of Alzheimer's disease, promotes an abnormal aggregation of tau
Authors: Ismael Santa-Maria, Félix Hernández, Joaquín Del Rio, Francisco J Moreno, Jesús Avila
Journal: Molecular Neurodegeneration (2007)

Alzheimer's disease (AD) is characterized by the presence of two histopathological hallmarks; the senile plaques, or extracellular deposits mainly composed of amyloid-beta peptide (Abeta), and the neurofibrillary tangles, or intraneuronal inclusions composed of hyperphosphorylated tau protein.Since Abeta aggregates are found in the pathological cases, several strategies are under way to develop drugs that interact with Abeta to reduce its assembly. One of them is 3-amino-1-propane sulfonic acid (Tramiprosate, 3-APS, Alzhemedtrade mark), that was developed as a sulfated glycosaminoglycan mimetic, that could interact with Abeta peptide, preventing its aggregation.However, little is known about the action of 3-APS on tau protein aggregation. In this work, we have tested the action of 3-APS on cell viability, microtubule network, actin organization and tau aggregation. Our results indicate that 3-APS favours tau aggregation, in tau transfected non-neuronal cells, and in neuronal cells. We also found that 3-APS does not affect the binding of tau to microtubules but may prevent the formation of tau-actin aggregates. We like to emphasize the importance of testing on both types of pathology (amyloid and tau) the potential drugs to be used for AD treatment.
Quantum structure and human thought
Authors: Diederik Aerts, Jan Broekaert, Liane Gabora, Sandro Sozzo
Journal: Behavioral and Brain Sciences (2013)

Abstract We support the authors' claims, except that we point out that also quantum structure different from quantum probability abundantly plays a role in human cognition. We put forward several elements to illustrate our point, mentioning entanglement, contextuality, interference, and emergence as effects, and states, observables, complex numbers, and Fock space as specific mathematical structures.
Allergy to <i>Diplotaxis erucoides</i> pollen: occupational sensitization and cross‐reactivity with other common pollens
Authors: P. García‐Ortega, B. Bartolomé, E. Enrique, P. Gaig, C. Richart
Journal: Allergy (2001)

Background: Diplotaxis erucoides is a common weed of the Brassicaceae family widespread in southern and central Europe. Methods: A total of 410 consecutive patients referred for allergy study of rhinoconjunctivitis and/or asthma were skin tested with D. erucoides pollen, 14 proving positive. A purified D. erucoides pollen extract was prepared to perform quantitative skin tests, provocation tests, immunoblotting, and EIA inhibition in the 14 sensitized patients. Results: Three patients, directly involved in viniculture, had rhinoconjunctivitis related to D. erucoides pollen. No D. erucoides ‐related symptoms were observed in most patients, who were also sensitized to Artemisia pollen. RAST was positive in 12/14 patients and nasal provocation tests in 9/12. The molecular masses of the most prevalent IgE‐binding proteins ranged from 26 to 27.5 and from 31 to 34 kDa. D. erucoides pollen inhibited the IgE‐binding of other sensitizing pollens in the three viniculture workers, whereas both Artemisia and D. erucoides pollen produced similar heterologous inhibition in the pooled serum of the remaining, nonclinically affected, D. erucoides ‐sensitized patients. Conclusions: D. erucoides pollen may be an important prevalent aeroallergen, particularly in rural areas. It may act as an occupational allergen in vineyard workers, in whom it seems to be the primary sensitizing agent, playing a secondary cross‐reactive role in other sensitized patients.
Airway resistance and atopy in preschool children with wheeze and cough
Authors: S.A. McKenzie, P.D. Bridge, M.J.R. Healy
Journal: European Respiratory Journal (2000)

The extent to which the measurement of airways resistance by the interrupter technique (Rint) distinguishes preschool children with previous wheeze from those with no respiratory symptoms and helps to classify subjects with persistent cough, was investigated. Rint was measured before and after salbutamol treatment in 82 children with recurrent wheeze, 58 with isolated cough and 48 with no symptoms (control subjects). Their mean age (range) was 3.7 yrs (2-&lt;5 yrs). Median baseline Rint was higher (p&lt;0.0001) in wheezers than in either coughers or control subjects (1.16, 0.94 and 0.88 kPa x L(-1) x s(-1) respectively); coughers did not differ significantly from control subjects (p=0.14). The median ratios of baseline to post-salbutamol measurements (bronchodilator response (BDR)) in the groups differed significantly (1.40, 1.27 and 1.07, p&lt; or =0.01 for all), suggesting that coughers occupy an intermediate position. A BDR ratio of &gt;1.22 had a specificity and sensitivity for wheeze of 80% and 76% respectively. Twenty-eight coughers had a BDR ratio &gt;1.22. Wheezers9 immunoglobulin E was inversely related to baseline Rint. It is concluded that measurements of airway resistance by the interrupter technique are useful for classifying preschool children with respiratory symptoms and could be used to monitor the effect of interventions. The relation between atopy and airways resistance suggests that they have separate roles in preschool wheezing. Coughers with a high bronchodilator response could represent "cough-variant" asthma in children who have baseline airway resistance by the interrupter technique measurements similar to control subjects. Whether these children develop classical asthma will only be known at follow-up later in childhood.
Monitoring of Singlet Oxygen Is Useful for Predicting the Photodynamic Effects in the Treatment for Experimental Glioma
Authors: Junkoh Yamamoto, Seiji Yamamoto, Toru Hirano, Shaoyi Li, Masayo Koide, Eiji Kohno, Mitsuo Okada, Chikanori Inenaga, Tsutomu Tokuyama, Naoki Yokota, Susumu Terakawa, Hiroki Namba
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Singlet oxygen (1O2) generated in photodynamic therapy (PDT) plays a very important role in killing tumor cells. Using a new near-IR photomultiplier tube system, we monitored the real-time production of 1O2 during PDT and thus investigated the relationship between the 1O2 production and photodynamic effects. Experimental Design: We did PDT in 9L gliosarcoma cells in vitro and in an experimental tumor model in vivo using 5-aminolevulinic acid and nanosecond-pulsed dye laser. During this time, we monitored 1O2 using this system. Moreover, based on the 1O2 monitoring, we set the different conditions of laser exposure and investigated whether they could affect the tumor cell death. Results: We could observe the temporal changes of 1O2 production during PDT in detail. At a low fluence rate the 1O2 signal gradually decreased with a low peak, whereas at a high fluence rate it decreased immediately with a high peak. Consequently, the cumulative 1O2 at a low fluence rate was higher, which thus induced a strong photodynamic effect. The proportion of apoptosis to necrosis might therefore be dependent on the peak and duration of the 1O2 signal. A low fluence rate tended to induce apoptotic change, whereas a high fluence rate tended to induce necrotic change. Conclusions: The results of this study suggested that the monitoring of 1O2 enables us to predict the photodynamic effect, allowing us to select the optimal laser conditions for each patient.
Stretch-Dependent Modulation of Contractility and Growth in Smooth Muscle of Rat Portal Vein
Authors: As’ad Zeidan, Ina Nordström, Karl Dreja, Ulf Malmqvist, Per Hellstrand
Journal: Circulation Research (2000)

Abstract —Increased intraluminal pressure of the rat portal vein in vivo causes hypertrophy and altered contractility in 1 to 7 days. We have used organ cultures to investigate mechanisms involved in this adaptation to mechanical load. Strips of rat portal vein were cultured for 3 days, either undistended or loaded by a weight. Length-force relations were shifted toward longer length in stretched cultured veins compared with freshly dissected veins, whereas the length-force relations of unstretched cultured veins were shifted in the opposite direction. This occurred after culture either with or without 10% FCS to promote growth. The wet weight of loaded veins increased by 56% in the presence of FCS, whereas that of undistended control veins increased by 24%. No weight increase was seen in serum-free culture. The dry/wet weight ratio decreased during culture with FCS but was not affected by stretch. Electron microscopy revealed increased cell cross-sectional area in stretched relative to unstretched veins, and protein contents were greater, as were [ 3 H]thymidine and [ 3 H]leucine incorporation rates. Growth responses were associated with the activation of stretch-sensitive extracellular signal–regulated kinases 1 and 2 and were inhibited by herbimycin A and PD 98059, inhibitors of extracellular signal–regulated kinases 1 and 2. The results demonstrate that by culture of whole vascular tissue, smooth muscle cells are maintained in the contractile phenotype and respond to stretch with a physiological adaptation involving hypertrophy/hyperplasia and remodeling of the contractile system, similar to that in vivo. Mechanical stimulation and growth factors are both required for functionally significant growth.
In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices
Authors: PW Barry, C O'Callaghan
Journal: European Respiratory Journal (1997)

Metered-dose inhalers (MDIs) are currently being reformulated to contain hydrofluoroalkanes (HFAs), which do not damage the Earth's ozone layer. As different formulations of inhaled drugs may behave differently when used with spacer devices, we wished to determine the amount of salbutamol available for inhalation from a conventional metered-dose inhaler (Ventolin) and a new HFA-containing formulation (Airomir), when used with two different spacers. A glass multistage liquid impinger was used to determine the amount of salbutamol delivered from the inhalers used with the Aerochamber and the Nebuhaler spacer devices. High speed video-recordings of inhaler actuation into air were made, and the speed of the aerosol and the aerosol cloud volume were measured. More salbutamol in small particles (&lt;5 microm) was delivered from the Airomir MDI than the Ventolin MDI, when used with the Aerochamber (40.4 (95% confidence interval (95% CI) 31.2-49.6) versus 19.5 (19.0-20.0) microg) and the Nebuhaler (42.1 (36.3-47.9) versus 24.6 (23.3-25.8) microg). The aerosol cloud from the Airomir MDI was slower than the Ventolin aerosol, and 60 ms after actuation had travelled 186 mm, whereas the Ventolin aerosol had travelled 320 mm. At the same time, the Airomir aerosol occupied a smaller volume than the Ventolin MDI (251 (213-288) versus 695 (608-782) cm3). The hydrofluoroalkane formulation delivers more salbutamol than the conventional formulation when used either with the Aerochamber or Nebuhaler spacer. This may be because less drug is deposited in the spacer from the hydrofluoroalkane formulation, which is emitted from the metered-dose inhaler at a slower speed and occupies a smaller volume than the conventional formulation. The observed difference in drug delivery may be important for patients changing formulations, and in severe asthma, where high doses of salbutamol may be administered through a spacer.
Nonuniform loss of regional flow reserve during myocardial ischemia in dogs.
Authors: D L Coggins, A E Flynn, R E Austin, G S Aldea, D Muehrcke, M Goto, J I Hoffman
Journal: Circulation Research (1990)

To determine whether coronary vasodilator reserve that persists during myocardial ischemia is present in all left ventricular regions, we measured regional blood flow in 192 left ventricular pieces (mean weight, 201 mg) in each of eight dogs by using radioactive microspheres while perfusing the left main coronary artery at 70, 50, 40, and 30 mm Hg. Flows were measured before and during adenosine infusion to determine flow reserve. Perfusion at 40 and 30 mm Hg produced ischemia in all dogs. At 70 mm Hg, 100% of left ventricular regions had significant flow reserve, compared with 92%, 55%, and 8% during perfusion at 50, 40, and 30 mm Hg, respectively. A greater amount of flow reserve and a greater number of regions responded to adenosine in the subepicardium than in the subendocardium at 50, 40, and 30 mm Hg. We conclude that coronary flow reserve persists in only a subset of left ventricular regions during ischemia and that the number of regions with persistent flow reserve decreases with perfusion pressure. These findings may best be explained by a model in which regional ischemia is a maximal coronary vasodilator and persistent pharmacological vasodilator reserve seen when global markers indicate ischemia simply reflects persistent endogenous flow reserve in myocardial regions not yet ischemic.
Identification of vascular postsynaptic alpha 1- and alpha 2-adrenoceptors in man.
Authors: K Jie, P van Brummelen, P Vermey, P B Timmermans, P A van Zwieten
Journal: Circulation Research (1984)

We studied postsynaptic alpha-adrenoceptors in human blood vessels by measuring the influence on forearm blood flow induced by intra-arterial infusions of selective alpha 1- and alpha 2-adrenoceptor agonists (methoxamine, B-HT 933, clonidine and guanfacine) and antagonists (doxazosin and yohimbine). The studies were done in healthy volunteers, and forearm blood flow was measured by plethysmography. All agonists produced a significant and dose-dependent vasoconstriction. The effect of B-HT 933 was completely abolished by the concomitant infusion of yohimbine, whereas it was hardly influenced by doxazosin. The effect of methoxamine was prevented by doxazosin and little influenced by yohimbine. The vasoconstriction by clonidine and guanfacine was partially prevented by both doxazosin and yohimbine. The single intra-arterial infusion of yohimbine, as well as doxazosin, resulted in vasodilation. These findings provide strong evidence for the existence of postsynaptic alpha 1- as well as alpha 2-adrenoceptors, both mediating vasoconstriction and contributing to basal vascular tone. The (patho-)physiological significance of this subdivision of alpha-adrenoceptors remains to be elucidated.
Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application?
Authors: James D. Brenton, Lisa A. Carey, Ahmed Ashour Ahmed, Carlos Caldas
Journal: Journal of Clinical Oncology (2005)

Profiling breast cancer with expression arrays has become common, and it has been suggested that the results from early studies will lead to understanding of the molecular differences between clinical cases and allow individualization of care. We critically review two main applications of expression profiling; studies unraveling novel breast cancer classifications and those that aim to identify novel markers for prediction of clinical outcome. Breast cancer may now be subclassified into luminal, basal, and HER2 subtypes with distinct differences in prognosis and response to therapy. However, profiling studies to identify predictive markers have suffered from methodologic problems that prevent general application of their results. Future work will need to reanalyze existing microarray data sets to identify more representative sets of candidate genes for use as prognostic signatures and will need to take into account the new knowledge of molecular subtypes of breast cancer when assessing predictive effects.
Implicit and explicit learning in a hybrid architecture of cognition
Authors: Christian Lebiere, Dieter Wallach
Journal: Behavioral and Brain Sciences (1999)

We present a theoretical account of implicit and explicit learning in terms of act-r , an integrated architecture of human cognition as a computational supplement to Dienes &amp; Perner's conceptual analysis of knowledge. Explicit learning is explained in act-r by the acquisition of new symbolic knowledge, whereas implicit learning amounts to statistically adjusting subsymbolic quantities associated with that knowledge. We discuss the common foundation of a set of models that are able to explain data gathered in several signature paradigms of implicit learning.
Characteristics of zinc binding to human red blood cell membranes
Authors: José Brandão‐Néto, William R. Bell
Journal: American Journal of Hematology (1994)

The objective of the present study was to standardize the analysis of zinc binding on human red blood cell (RBC) membranes in 20 normal adults. The displacement studies revealed that at the maximal stable zinc concentration tested (600 microM), 57% (mean) of the bound 65Zn was displaced and to displace half maximal 65Zn, the stable zinc concentration was 300 microM. Scatchard plots revealed two classes of binding sites for zinc on RBC membranes: one with higher affinity, Kd = 1.20 x 10(-5) M (site I), and the other with lower affinity, Kd = 2.77 x 10(-4) M (site II). Binding sites occupancy was 97% means and 58.5% means for sites I and II, respectively. The displacement was affected by temperature, membrane protein concentration, freezing, thawing, and dialysis. Other metal cations, including Co++, Fe++, and Mn++, had very little effect on 65Zn displacement, in contrast copper displaced 65Zn from its binding sites on RBC membranes. Zinc binding to RBC membranes was rapid and readily reversible in a dynamic equilibrium with its binding sites. It is anticipated that this method will be applicable to studies of a wide variety of diseases specifically related to zinc metabolism in humans as well as in animals.