tbuckley/cabot-search huggingface dataset:
Pharmacodynamics and Pharmacokinetics of Eptifibatide in Patients With Acute Coronary Syndromes
Authors: Barbara E. Tardiff, Lisa K. Jennings, Robert A. Harrington, Daniel Gretler, Richard F. Potthoff, David A. Vorchheimer, Paul R. Eisenberg, A. Michael Lincoff, Marino Labinaz, Diane M. Joseph, Mark F. McDougal, Neal S. Kleiman
Journal: Circulation (2001)

Platelet deposition and aggregation are central to the pathogenesis of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic effects of the platelet glycoprotein IIb/IIIa antagonist eptifibatide have been delineated in healthy subjects but not in patients with ACS. We assessed effects of eptifibatide on ex vivo platelet aggregation in patients enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy (PURSUIT) trial of ACS.Patients were randomly assigned to an intravenous bolus (180 microgram/kg) and 72-hour infusion of eptifibatide (2.0 microgram/kg per minute, n=48) or placebo (n=50). We assessed correlations of plasma eptifibatide levels with receptor occupancy and inhibition of ex vivo platelet aggregation at 5 minutes and 1, 4, 24, 48, and 72 hours during treatment and 4 and 8 hours after termination of infusion. Blood was collected in buffered citrate and D-phenylalanyl-L-prolyl-L-arginine chloromethylketone anticoagulants. Although eptifibatide produced profound, prolonged inhibition of platelet aggregation during therapy, aggregation appeared to recover partially by 4 hours after the bolus. The aggregation response was greater with thrombin receptor agonist peptide versus ADP stimulation; inhibition of platelet aggregation was greater in blood samples anticoagulated with citrate versus D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK). Plasma eptifibatide levels correlated significantly with receptor occupancy but not with inhibition of platelet aggregation.A bolus and infusion of eptifibatide inhibits platelet aggregation profoundly in patients with ACS and is followed by brief, partial recovery. These results enhance our understanding of the relation between pharmacodynamic and clinical effects of eptifibatide in such patients and may have important implications for its use in percutaneous interventions.
Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy
Authors: Markus Mandler, Elvira Valera, Edward Rockenstein, Michael Mante, Harald Weninger, Christina Patrick, Anthony Adame, Sabine Schmidhuber, Radmila Santic, Achim Schneeberger, Walter Schmidt, Frank Mattner, Eliezer Masliah
Journal: Molecular Neurodegeneration (2015)

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia and dysautonomia. Histopathologically, the hallmark of MSA is the abnormal accumulation of alpha-synuclein (α-syn) within oligodendroglial cells, leading to neuroinflammation, demyelination and neuronal death. Currently, there is no disease-modifying treatment for MSA. In this sense, we have previously shown that next-generation active vaccination technology with short peptides, AFFITOPEs®, was effective in two transgenic models of synucleinopathies at reducing behavioral deficits, α-syn accumulation and inflammation. In this manuscript, we used the most effective AFFITOPE® (AFF 1) for immunizing MBP-α-syn transgenic mice, a model of MSA that expresses α-syn in oligodendrocytes. Vaccination with AFF 1 resulted in the production of specific anti-α-syn antibodies that crossed into the central nervous system and recognized α-syn aggregates within glial cells. Active vaccination with AFF 1 resulted in decreased accumulation of α-syn, reduced demyelination in neocortex, striatum and corpus callosum, and reduced neurodegeneration. Clearance of α-syn involved activation of microglia and reduced spreading of α-syn to astroglial cells. This study further validates the efficacy of vaccination with AFFITOPEs® for ameliorating the neurodegenerative pathology in synucleinopathies.
6-Thioguanosine Diphosphate and Triphosphate Levels in Red Blood Cells and Response to Azathioprine Therapy in Crohn’s Disease
Authors: M NEURATH, R KIESSLICH, U TEICHGRABER, C FISCHER, U HOFMANN, M EICHELBAUM, P GALLE, M SCHWAB
Journal: Clinical Gastroenterology and Hepatology (2005)
Staufen- and FMRP-Containing Neuronal RNPs Are Structurally and Functionally Related to Somatic P Bodies
Authors: Scott A. Barbee, Patricia S. Estes, Anne-Marie Cziko, Jens Hillebrand, Rene A. Luedeman, Jeff M. Coller, Nick Johnson, Iris C. Howlett, Cuiyun Geng, Ryu Ueda, Andrea H. Brand, Sarah F. Newbury, James E. Wilhelm, Richard B. Levine, Akira Nakamura, Roy Parker, Mani Ramaswami
Journal: Neuron (2006)
Lowest Systolic Blood Pressure Is Associated with Stroke in Stages 3 to 4 Chronic Kidney Disease
Authors: Daniel E. Weiner, Hocine Tighiouart, Andrew S. Levey, Essam Elsayed, John L. Griffith, Deeb N. Salem, Mark J. Sarnak
Journal: Journal of the American Society of Nephrology (2007)

Hypertension is a risk factor for stroke in the general population, whereas in hemodialysis patients, higher systolic BP (SBP) may be protective. Therefore, this study evaluated the relationship between SBP and stroke in individuals with and without chronic kidney disease (CKD) to assess whether this altered relationship exists in earlier stages of CKD. A secondary evaluation of two community-based, longitudinal, limited-access data sets was performed: Atherosclerosis Risk in Communities and Cardiovascular Health Study. CKD was defined as estimated GFR <60 ml/min per 1.73 m(2). The primary study outcome was definite or probable incident stroke. We used Cox proportional hazards models to assess the relationship between CKD and stroke, focusing on the role of SBP. Among 20,358 individuals studied, 1549 (7.6%) had CKD. During a median duration of 111 mo, 1029 (5.1%) individuals had a stroke. CKD and elevated SBP both independently predicted incident stroke (hazard ratio [HR] 1.22 [95% confidence interval [CI]1.02 to 1.44] and HR 1.18 [95% CI 1.14 to 1.21] per 10-mmHg rise, respectively). Individuals with CKD had a J-shaped relationship with stroke outcomes such that those with SBP <120 mmHg were at significantly increased risk compared with individuals with CKD and SBP 120 to 129 mmHg (HR 2.51; 95% CI 1.30 to 4.87); risk increased for BP >130 mmHg in CKD. This J shape was not seen in individuals without CKD. CKD and elevated SBP are independent risk factors for incident stroke. In CKD, individuals with the lowest BP are at increased risk for stroke. This pattern is not seen in the general population.
THE ACID-BASE COMPOSITION OF GASTRIC SECRETIONS
Authors: James L. Gamble, Monroe A. McIver
Journal: The Journal of Experimental Medicine (1928)

The chief inorganic factors in secretions obtained from isolated pouches constructed in the fundus and in the pyloric antrum of the cat's stomach were found to be chloride ion and fixed base. In a series of samples obtained from the fundic pouch, chloride ion was approximately stationary at 165 cc. 0.1 N per 100 cc. During digestion of food in the stomach, secretions from the pouch contained fixed base in amounts varying considerably from an average of 47 cc. 0.1 N per 100 cc. Material allowed to remain in the pouch after the completion of food digestion in the stomach showed an increasing content of fixed base, to as much as 140 cc. 0.1 N per 100 cc. A stationary total ionic content of secretions of the fundus is thus seen to be sustained by the chloride ion concentration, and changes in hydrogen ion concentration to be caused by variation of fixed base. The differing amounts of fixed base found are regarded as probably due to admixture of a mucous secretion with the juice from the fundic glands. The alkaline secretion taken from a pyloric pouch contained fixed base in excess of chloride ion. Variation of fixed base in the secretions from the fundic pouch were found to be referable to change in sodium content, the smaller factor, potassium, remaining approximately constant at about the value found in material from the pyloric pouch. This suggests that the mucous secretion of the fundus has the same composition as that produced by the pyloric antrum. These data will serve to explain the extensive withdrawal of fixed base, as well as of chloride ion, from the blood plasma in the presence of circumstances causing a continued loss of stomach secretions.
Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis
Authors: Jie Li, Oluwole Fadare, Li Xiang, Beihua Kong, Wenxin Zheng
Journal: Journal of Hematology & Oncology (2012)

Recent morphologic and molecular genetic studies have led to a paradigm shift in our conceptualization of the carcinogenesis and histogenesis of pelvic (non-uterine) serous carcinomas. It appears that both low-grade and high-grade pelvic serous carcinomas that have traditionally been classified as ovarian in origin, actually originate, at least in a significant subset, from the distal fallopian tube. Clonal expansions of the tubal secretory cell probably give rise to serous carcinomas, and the degree of ciliated conversion is a function of the degree to which the genetic hits deregulate normal differentiation. In this article, the authors review the evidentiary basis for aforementioned paradigm shift, as well as its potential clinical implications.
Translocations Involving the Immunoglobulin Heavy Chain Gene Locus Predict Better Survival in Gastric Diffuse Large B-Cell Lymphoma
Authors: Shotaro Nakamura, Hongtao Ye, Chris M. Bacon, Alison Goatly, Hongxiang Liu, Lucy Kerr, Alison H. Banham, Berthold Streubel, Takashi Yao, Masazumi Tsuneyoshi, Antonella Savio, Morishige Takeshita, Peggy Dartigues, Agnès Ruskoné-Fourmestraux, Takayuki Matsumoto, Mitsuo Iida, Ming-Qing Du
Journal: Clinical Cancer Research (2008)

The pathogenesis and clinical heterogeneity of gastric diffuse large B-cell lymphoma (DLBCL) are poorly understood. We have comprehensively investigated the incidence and clinical significance of lymphoma-associated chromosomal translocations, particularly those involving the immunoglobulin heavy chain (IGH) gene locus, in a large series of gastric DLBCL.One hundred forty-one cases of primary gastric DLBCL [58 with mucosa-associated lymphoid tissue (MALT) lymphoma and 83 without MALT lymphoma] were enrolled. Translocations involving BCL6, c-MYC, FOXP1, MALT1, and IGH were investigated using interphase fluorescence in situ hybridization. In positive cases, additional fluorescence in situ hybridization was done with appropriate probes for potential partner genes. Cases were classified into germinal center B-cell-like (GCB) or non-GCB subgroups by immunophenotyping with CD10, BCL6, and MUM1.Translocations involving IGH were detected in 36 (32%) of 111 cases; their partner genes included BCL6 (n = 10), c-MYC (n = 5), and FOXP1 (n = 3) but remained unknown in the remaining 18 cases. t(14;18)/IGH-BCL2, t(14;18)/IGH-MALT1, and t(1;14)/BCL10-IGH were not detected in any case. t(11;18)/API2-MALT1 was detected in none of the cases, except for one case of DLBCL with MALT lymphoma, which showed positive signals only in MALT lymphoma cells. IGH-involved translocation was associated with younger age but not with any other clinicopathologic factors including GCB or non-GCB immunophenotypes. Cox multivariate analysis revealed that IGH-involved translocation, in addition to younger age and early stage, was an independent prognostic factor for better overall and EFSs.IGH-involved translocations are frequent in gastric DLBCL and seem to identify cases with favorable prognosis.
Neuromuscular activity and force production during slide-based and stationary ergometer rowing
Authors: A Vinther, T Alkjaer, I-L Kanstrup, B Zerahn, C Ekdahl, K Jensen, A Holsgaard-Larsen, P Aagaard
Journal: British Journal of Sports Medicine (2011)

Background The type of rowing ergometer may influence the injury risk in rowers. Overuse rowing injuries (ie, rib stress fractures and low back pain) may be related to the timing and magnitude of neuromuscular activity and handle force production, respectively. Objective To investigate neuromuscular activity and force production profile during slide-based and stationary ergometer rowing. Design Biomechanical cross-over study. Setting Danish National Rowing Team. Participants 14 male (M) and eight female (F) rowers. Intervention Ergometer rowing with and without slides in a randomised order at matched exercise intensity. Main outcome measurements Timing and magnitude of: (1) Normalised Electromyography (EMG) from selected thoracic and leg muscles. (2) Peak handle force (PF) including rate of force development (RFD). Results Slide-based ergometer rowing decreased the magnitude of neuromuscular activity in m. vastus lateralis from 59/57% (M/F) to 51/52% EMGmax in the initial drive phase (p&lt;0.01/0.05) and from 20/17% to 7/7% EMGmax in the late recovery phase (p&lt;0.01) while Ankle dorsiflexors (M, F) and m. serratus anterior (M) showed increased neuromuscular activity (p&lt;0.05) during the late recovery phase. EMG timing remained unchanged and no changes in magnitude were observed in other thoracic muscles. RFD (at 50–70% of PF) decreased (21%) in M (p&lt;0.05) while PF decreased 8.4/3.1% (M/F) (p&lt;0.001/0.05). PF and maximal shoulder retractor neuromuscular activity always occurred in the second quartile of the drive phase supporting previously suggested rib stress fracture injury mechanisms. Conclusion Slide-based ergometer rowing affected neuromuscular activity in the leg muscles more than thoracic muscle activity. The reduced knee extensor neuromuscular activity in the catch phase may partly explain the observed reduction in peak force, which in addition to the decreased RFD (M), is likely to result in reduced loading of the ribs and spine. Prospective studies are needed to elucidate if long-term slide-based ergometer rowing leads to reduced injury incidence.
Quantifying physical activity in daily life with questionnaires and motion sensors in COPD
Authors: F. Pitta, T. Troosters, V. S. Probst, M. A. Spruit, M. Decramer, R. Gosselink
Journal: European Respiratory Journal (2006)

Accurate assessment of the amount and intensity of physical activity in daily life is considered very important due to the close relationship between physical activity level, health, disability and mortality. For this reason, assessment of physical activity in daily life has gained interest in recent years, especially in sedentary populations, such as patients with chronic obstructive pulmonary disease (COPD). The present article aims to compare and discuss the two kinds of instruments more commonly used to quantify the amount of physical activity performed by COPD patients in daily life: subjective methods (questionnaires, diaries) and motion sensors (electronic or mechanical methods). Their characteristics are summarised and evidence of their validity, reliability and sensitivity is discussed, when available. Subjective methods have practical value mainly in providing the patients' view on their performance in activities of daily living and functional status. However, care must be taken when using subjective methods to accurately quantify the amount of daily physical activity performed. More accurate information is likely to be available with motion sensors rather than questionnaires. The selection of which motion sensor to use for quantification of physical activity in daily life should depend mainly on the purpose of its use.
The Bioreductive Prodrug PR-104A Is Activated under Aerobic Conditions by Human Aldo-Keto Reductase 1C3
Authors: Christopher P. Guise, Maria R. Abbattista, Rachelle S. Singleton, Samuel D. Holford, Joanna Connolly, Gabi U. Dachs, Stephen B. Fox, Robert Pollock, Justin Harvey, Parry Guilford, Fernando Doñate, William R. Wilson, Adam V. Patterson
Journal: Cancer Research (2010)

PR-104, currently in phase II clinical trials, is a phosphate ester pre-prodrug which is converted in vivo to its cognate alcohol, PR-104A, a prodrug designed to exploit tumor hypoxia. Bioactivation occurs via one-electron reduction to DNA crosslinking metabolites in the absence of oxygen. However, certain tumor cell lines activate PR-104A in the presence of oxygen, suggesting the existence of an aerobic nitroreductase. Microarray analysis identified a cluster of five aldo-keto reductase (AKR) family members whose expressions correlated with aerobic metabolism of PR-104A. Plasmid-based expression of candidate genes identified aldo-keto reductase 1C3 as a novel nitroreductase. AKR1C3 protein was detected by Western blot in 7 of 23 cell lines and correlated with oxic PR-104A metabolism, an activity which could be partially suppressed by Nrf2 RNAi knockdown (or induced by Keap1 RNAi), indicating regulation by the ARE pathway. AKR1C3 was unable to sensitize cells to 10 other bioreductive prodrugs and was associated with single-agent PR-104 activity across a panel of 9 human tumor xenograft models. Overexpression in two AKR1C3-negative tumor xenograft models strongly enhanced PR-104 antitumor activity. A population level survey of AKR1C3 expression in 2,490 individual cases across 19 cancer types using tissue microarrays revealed marked upregulation of AKR1C3 in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma. A survey of normal tissue AKR1C3 expression suggests the potential for tumor-selective PR-104A activation by this mechanism. These findings have significant implications for the clinical development of PR-104.
White cell scanning has a role in imaging small and large bowel
Authors: A P Poullis
Journal: Gut (2006)

I enjoyed the article by Albert et al ( Gut 2005; 52 :1721–7) comparing newly emerging imaging modalities for the assessment and detection of small bowel Crohn’s disease, an area of the gastrointestinal tract that is often difficult to adequately image, assess, and biopsy.

However, their …
Hilar and mediastinal lymphadenopathy in the limited form of Wegener's granulomatosis.
Authors: V M Gutierrez-Rave, M A Ayerza
Journal: Thorax (1991)

A patient with the limited form of Wegener9s granulomatosis is reported. The case is unusual because of hilar and mediastinal lymphadenopathy, severe ulceration of the respiratory and digestive tracts, and the rapidly fatal outcome.
Therapeutic Cancer Vaccines: Current Status and Moving Forward
Authors: J. Schlom
Journal: JNCI Journal of the National Cancer Institute (2012)

Concurrent with US Food and Drug Administration (FDA) approval of the first therapeutic cancer vaccine, a wide spectrum of other cancer vaccine platforms that target a diverse range of tumor-associated antigens is currently being evaluated in randomized phase II and phase III trials. The profound influence of the tumor microenvironment and other immunosuppressive entities, however, can limit the effectiveness of these vaccines. Numerous strategies are currently being evaluated both preclinically and clinically to counteract these immunosuppressive entities, including the combined use of vaccines with immune checkpoint inhibitors, certain chemotherapeutics, small-molecule targeted therapies, and radiation. The potential influence of the appropriate patient population and clinical trial endpoint in vaccine therapy studies is discussed, as well as the potential importance of biomarkers in future directions of this field.
THE NODULAR DERMAL ALLERGIDES OF GOUGEROT.
Authors: H. GOUGEROT, B. DUPERRAT
Journal: British Journal of Dermatology (1954)

Journal Article THE NODULAR DERMAL ALLERGIDES OF GOUGEROT. Get access H. GOUGEROT, H. GOUGEROT Search for other works by this author on: Oxford Academic Google Scholar B. DUPERRAT B. DUPERRAT Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 66, Issue 8-9, 1 August 1954, Pages 283–286, https://doi.org/10.1111/j.1365-2133.1954.tb12635.x Published: 01 August 1954
Meyerian psychobiology, personality development, and the role of life experiences
Authors: Michael Rutter
Journal: American Journal of Psychiatry (1986)

The psychobiological life history approach to psychiatry is perhaps the most important of Adolf Meyer's contributions to psychiatric thinking. The author outlines the implications of that approach for current concepts and practice. He reviews the literature regarding the causative role of life experiences in the genesis of psychiatric disorder, the extent to which the effects of stressors are situation-specific, the effects of stress on the organism, the reason for individual variations in the response to stress, and the cause of life stressors.
History of Click-Speaking Populations of Africa Inferred from mtDNA and Y Chromosome Genetic Variation
Authors: S. A. Tishkoff, M. K. Gonder, B. M. Henn, H. Mortensen, A. Knight, C. Gignoux, N. Fernandopulle, G. Lema, T. B. Nyambo, U. Ramakrishnan, F. A. Reed, J. L. Mountain
Journal: Molecular Biology and Evolution (2007)

Little is known about the history of click-speaking populations in Africa. Prior genetic studies revealed that the click-speaking Hadza of eastern Africa are as distantly related to click speakers of southern Africa as are most other African populations. The Sandawe, who currently live within 150 km of the Hadza, are the only other population in eastern Africa whose language has been classified as part of the Khoisan language family. Linguists disagree on whether there is any detectable relationship between the Hadza and Sandawe click languages. We characterized both mtDNA and Y chromosome variation of the Sandawe, Hadza, and neighboring Tanzanian populations. New genetic data show that the Sandawe and southern African click speakers share rare mtDNA and Y chromosome haplogroups; however, common ancestry of the 2 populations dates back >35,000 years. These data also indicate that common ancestry of the Hadza and Sandawe populations dates back >15,000 years. These findings suggest that at the time of the spread of agriculture and pastoralism, the click-speaking populations were already isolated from one another and are consistent with relatively deep linguistic divergence among the respective click languages.
The multiple risk factor intervention trial
Authors: M A Mishkel
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The Journalis to be commended for its publication of the MRFIT mortality report. How many studies that do not show positive results are ever published?The Journalis also to be commended for the call to "responsible debate on controversial issues" contained in the accompanying editorial by Dr Lundberg. As to the MRFIT report itself, the reason for the striking failure of the trial lies in its erroneous basic assumption that reductions in CHD mortality would result from reductions in the three so-called major risk factors—cigarette smoking, high levels of BP, and serum cholesterol (SC). The MRFIT program failed to achieve an anticipated greater reduction in the overall CHD mortality rate in the special intervention (SI) group than in the control group receiving usual care (UC), despite the fact that the risk factor-reduction goals were essentially met. During the follow-up period, the SI group showed a
"Strategic vacuum" after end of NHS London threatens patient care in the capital
Authors: Z. Kmietowicz
Journal: BMJ (2011)

The government needs to spell out who will be responsible for coordinating health services across London when the capital’s strategic health authority is abolished in April 2012, says the healthcare think tank the King’s Fund.

A report from the fund warns that the situation raises “a real risk of declining financial performance and a failure to tackle unacceptable variations in the quality of care in the reformed NHS.”

The Health and Social Care Bill, which is currently before parliament, does not deal with what the fund refers to as “a strategic vacuum” in the coordination of London’s health services. …