tbuckley/cabot-search huggingface dataset:
A review of the pharmacology, pharmacokinetics and behavioral effects of procaine in thoroughbred horses.
Authors: T. Tobin, J. W. Blake
Journal: British Journal of Sports Medicine (1976)

Since procaine has both local anaesthetic and central stimulant actions its presence in the blood or urine of racing horses is forbidden. After rapid intravenous injection of procaine HC1 (2.5 mg/Kg) in thoroughbred mares plasma levels of this drug fell rapidly (t 1/2 alpha = 5 min) and then more slowly (t 1/2 beta = 50.2 min). These kinetics were well fitted by a two compartment open model (Model I). This model gave an apparent Vdbeta for procaine in the horse of about 3,500 litres. Since procaine was about 45% bound to equine plasma protein this gives a true Vdbeta for procaine of about 6,500 litres. After subcutaneous injection of procaine HC1 (3.3 mg/Kg) plasma levels peaked at about 400 ng/ml and then declined with a half-life of about 75 minutes. These data were well fitted by Model I when this was modified to include simple first order absorption (K = 0.048 min-1) from the subcutaneous injection site (Model II). After intramuscular injection of procaine penicillin (33,000 I.U./Kg) plasma levels reached a peak at about 270 ng/ml and then declined with a half-life of about 9 hours. These data were approximately fitted by Model II assuming a first order rate constant for absorption of procaine of 0.0024 min-1. After intramuscular injection of procaine HC1 (10 mg/Kg) plasma levels of procaine peaked rapidly at about 600 ng/ml but thereafter declined slowly (+ 1/2 = 2 hours). A satisfactory pharmaco-kinetic model for this intramuscular data could not be developed. An approximation of these data was obtained by assuming the existence of two intramuscular drug compartments, one containing readily absorbable drug and the other poorly absorbable drug (Model III). After intra-articular administration of procaine (0.33 mg/Kg) plasma levels of this drug reached a peak at about 17 ng/ml and then declined with a half-life of about 2 hours. These data were not modelled.
Evolutionary Patterns of Microrna Expression Through the Course of Disease and Therapy in Recurrent Breast Cancer
Authors: M. Dadiani, N. Bossel, S. Paluch-Shimon, S. Kahana-Edwin, A. Yosepovich, E. Nili Gal-Yam, I. Barshack, R. Berger, E. Domany, B. Kaufman
Journal: Annals of Oncology (2014)
Human B cell differentiation. II. Pokeweed mitogen-responsive B cells belong to a surface immunoglobulin D-negative subpopulation.
Authors: T Kuritani, M D Cooper
Journal: The Journal of Experimental Medicine (1982)

Surface immunoglobulin D (IgD)-positive lymphocytes precoated with monoclonal anti-delta antibody were selectively removed from blood mononuclear cell preparations by "panning" and by fluorescence-activated cell sorter. The depletion of sIgD+ cells did not significantly affect plasma cell responses to pokeweed mitogen PWM). PWM-responsive B cells lacking sIgD and mouse erythrocyte receptors preferentially sedimented in lower density fractions of a discontinuous Percoll gradient, and sIgD-negative B cells were found to have a larger mean diameter than IgD-positive cells. We conclude that PWM-responsive B cells represent a distinct subpopulation of relatively large cells that have ceased to express receptors for mouse erythrocytes and surface IgD.
A−β− Subtype of Ketosis-Prone Diabetes Is Not Predominantly a Monogenic Diabetic Syndrome
Authors: Wade C. Haaland, Diane I. Scaduto, Mario R. Maldonado, Dena L. Mansouri, Ramaswami Nalini, Dinakar Iyer, Sanjeet Patel, Anu Guthikonda, Christiane S. Hampe, Ashok Balasubramanyam, Michael L. Metzker
Journal: Diabetes Care (2009)

OBJECTIVE Ketosis-prone diabetes (KPD) is an emerging syndrome that encompasses several distinct phenotypic subgroups that share a predisposition to diabetic ketoacidosis. We investigated whether the A−β− subgroup of KPD, characterized by complete insulin dependence, absent β-cell functional reserve, lack of islet cell autoantibodies, and strong family history of type 2 diabetes, represents a monogenic form of diabetes. RESEARCH DESIGN AND METHODS Over 8 years, 37 patients with an A−β− phenotype were identified in our longitudinally followed cohort of KPD patients. Seven genes, including hepatocyte nuclear factor 4A (HNF4A), glucokinase (GCK), HNF1A, pancreas duodenal homeobox 1 (PDX1), HNF1B, neurogenic differentiation 1 (NEUROD1), and PAX4, were directly sequenced in all patients. Selected gene regions were also sequenced in healthy, unrelated ethnically matched control subjects, consisting of 84 African American, 96 Caucasian, and 95 Hispanic subjects. RESULTS The majority (70%) of the A−β− KPD patients had no significant causal polymorphisms in either the proximal promoter or coding regions of the seven genes. The combination of six potentially significant low-frequency, heterozygous sequence variants in HNF-1α (A174V or G574S), PDX1 (putative 5′–untranslated region CCAAT box, P33T, or P239Q), or PAX4 (R133W) were found in 27% (10/37) of patients, with one additional patient revealing two variants, PDX1 P33T and PAX4 R133W. The A174V variant has not been previously reported. CONCLUSIONS Despite its well-circumscribed, robust, and distinctive phenotype of severe, nonautoimmune-mediated β-cell dysfunction, A−β− KPD is most likely not a predominantly monogenic diabetic syndrome. Several A−β− KPD patients have low-frequency variants in HNF1A, PDX1, or PAX4 genes, which may be of functional significance in their pathophysiology.
Postoperative Surveillance Recommendations for Early Stage Colon Cancer Based on Results From the Clinical Outcomes of Surgical Therapy Trial
Authors: Vassiliki L. Tsikitis, Kishore Malireddy, Erin A. Green, Brent Christensen, Richard Whelan, Jace Hyder, Peter Marcello, Sergio Larach, David Lauter, Daniel J. Sargent, Heidi Nelson
Journal: Journal of Clinical Oncology (2009)

Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB and III) colon cancer. We hypothesized that stage I and IIA colon cancer patients would experience similar benefits.
Motivation rather than imitation determined the appearance of language
Authors: Pavel N. Prudkov
Journal: Behavioral and Brain Sciences (2005)

Arbib derives the origin of language from the emergence of a complex imitation system; however, it is unlikely that this complication could occur without a prior complicating within the imitated systems. This means that Arbib's hypothesis is not correct, because the other systems determined the appearance of language. In my opinion, language emerged when the motivational system became able to support goal-directed processes with no innate basis.
Implantable transvenous cardioverter-defibrillators.
Authors: G H Bardy, B Hofer, G Johnson, P J Kudenchuk, J E Poole, G L Dolack, M Gleva, R Mitchell, D Kelso
Journal: Circulation (1993)

Implantable transvenous cardioverter-defibrillators offer a significant opportunity to decrease procedural morbidity and medical costs in the care of patients with life-threatening ventricular arrhythmias who otherwise would have required a sternotomy or thoracotomy for device insertion. The purpose of this study was to examine prospectively the safety, efficacy, and limitations associated with the use of a transvenously implanted, tiered-therapy cardioverter-defibrillator with antitachycardia pacing function in a consecutive population of 84 ventricular fibrillation (VF) and sustained ventricular tachycardia (VT) survivors.The index arrhythmia promoting transvenous cardioverter-defibrillator implantation was VF in 41 patients, VT in 27, and both VF and VT in 16. In each patient, transvenous defibrillation via a coronary sinus, a right ventricular, a superior vena caval, and/or a subcutaneous chest patch lead system was attempted. The pulsing methods used include two-electrode single-pathway pulsing or three-electrode dual-pathway simultaneous or sequential pulsing. A transvenous cardioverter-defibrillator was inserted if the defibrillation threshold (DFT) was < or = 20 J. Successful implantation of a transvenous cardioverter-defibrillator was possible in 80 of 84 (95%) patients. The mean implant DFT was 10.9 +/- 4.8 J. After cardioverter-defibrillator implantation, all patients were extubated in the operating room and sent to a standard telemetry ward for monitoring. No patient suffered a postoperative pulmonary complication or perioperative flurry of cardiac arrhythmias. Postoperative complications included lead dislodgments in eight, transient long thoracic nerve injury in one, asymptomatic left subclavian vein occlusion in two, asymptomatic small pericardial effusion in one, subcutaneous patch pocket hematomas in four, pulse generator pocket infection in one, and lead fracture in one. As experience was gained with the procedure, it was routine to discharge patients 3 days after surgery. The mean hospital stay was 6.0 +/- 2.4 days. Upon discharge, all patients returned to their prehospital activities including those with complications except for the patient with a pocket infection, who required intravenous antibiotic therapy. Patient survival using an intention-to-treat analysis was 98% over an 11 +/- 7-month follow-up period. During this time period, 31 of the 80 patients (39%) with transvenous lead systems were successfully treated by their device for sustained VT or VF. Antitachycardia pacing was used in 424 episodes of monomorphic VT and was successful in 371 (88%). All episodes of VF were aborted by the device. Antiarrhythmic drugs were used after device implantation in only eight of 80 patients (10%).Transvenous cardioverter-defibrillator implantation is practical in most candidates. Implant DFTs are usually low, surgical morbidity and postoperative complications are modest, therapy of VT and VF is efficient, and survival is excellent.
Ancient genomic architecture for mammalian olfactory receptor clusters.
Authors: Ronny Aloni, Tsviya Olender, Doron Lancet
Journal: Genome biology (2006)

Abstract Background Mammalian olfactory receptor (OR) genes reside in numerous genomic clusters of up to several dozen genes. Whole-genome sequence alignment nets of five mammals allow their comprehensive comparison, aimed at reconstructing the ancestral olfactory subgenome. Results We developed a new and general tool for genome-wide definition of genomic gene clusters conserved in multiple species. Syntenic orthologs, defined as gene pairs showing conservation of both genomic location and coding sequence, were subjected to a graph theory algorithm for discovering CLICs (clusters in conservation). When applied to ORs in five mammals, including the marsupial opossum, more than 90% of the OR genes were found within a framework of 48 multi-species CLICs, invoking a general conservation of gene order and composition. A detailed analysis of individual CLICs revealed multiple differences among species, interpretable through species-specific genomic rearrangements and reflecting complex mammalian evolutionary dynamics. One significant instance involves CLIC #1, which lacks a human member, implying the human-specific deletion of an OR cluster, whose mouse counterpart has been tentatively associated with isovaleric acid odorant detection. Conclusion The identified multi-species CLICs demonstrate that most of the mammalian OR clusters have a common ancestry, preceding the split between marsupials and placental mammals. However, only two of these CLICs were capable of incorporating chicken OR genes, parsimoniously implying that all other CLICs emerged subsequent to the avian-mammalian divergence.
EGFR-Homing dsRNA Activates Cancer-Targeted Immune Response and Eliminates Disseminated EGFR-Overexpressing Tumors in Mice
Authors: Alexei Shir, Manfred Ogris, Wolfgang Roedl, Ernst Wagner, Alexander Levitzki
Journal: Clinical Cancer Research (2011)

The cause of most cancer deaths is incurable dissemination of cancer cells into vital organs. Current systemic therapies for disseminated cancers provide limited efficacy and are often accompanied by toxic side effects. We have recently shown that local application of epidermal growth factor receptor (EGFR)-targeted polyinosine-cytosine (polyIC) eradicates preestablished EGFR-overexpressing tumors. Here we show for the first time the high efficiency of systemic application of polyIC/melittin-polyethyleneimine-polyethyleneglycol-EGF (polyIC/MPPE) in combination with human immune cells.Cancer-targeted activation of immune cells was examined in vitro and in vivo following transfection with polyIC/MPPE. The therapeutic efficiency of the strategy was then examined on disseminated EGFR-overexpressing tumors grown in severe combined immunodeficient (SCID) mice.Intravenous delivery of polyIC/MPPE followed by intraperitoneal injection of peripheral blood mononuclear cells induced the complete cure of SCID mice with preestablished disseminated EGFR-overexpressing tumors, with no adverse toxic effects. The immune cells and the cytokines they produce are localized to the tumor site of the treated animal and contribute decisively to the demise of the tumor cells. The immune system homes to the tumors, due to the chemokines produced by the internalized polyIC.The EGFR-homing vector loaded with polyIC can be used to treat and possibly cure patients with disseminated EGFR-overexpressing tumors. The possibility of adopting this strategy to treat other tumors that express a protein capable of ligand induced internalization is discussed.
Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2
Authors: Jason D Ulrich, Mary Beth Finn, Yaming Wang, Alice Shen, Thomas E Mahan, Hong Jiang, Floy R Stewart, Laura Piccio, Marco Colonna, David M Holtzman
Journal: Molecular Neurodegeneration (2014)

Recent genome-wide association studies linked variants in TREM2 to a strong increase in the odds of developing Alzheimer’s disease. The mechanism by which TREM2 influences the susceptibility to Alzheimer’s disease is currently unknown. TREM2 is expressed by microglia and is thought to regulate phagocytic and inflammatory microglial responses to brain pathology. Given that a single allele of variant TREM2, likely resulting in a loss of function, conferred an increased risk of developing Alzheimer’s disease, we tested whether loss of one functional trem2 allele would affect Aβ plaque deposition or the microglial response to Aβ pathology in APPPS1-21 mice. There was no significant difference in Aβ deposition in 3-month old or 7-month old APPPS1-21 mice expressing one or two copies of trem2. However, 3-month old mice with one copy of trem2 exhibited a marked decrease in the number and size of plaque-associated microglia. While there were no statistically significant differences in cytokine levels or markers of microglial activation in 3- or 7-month old animals, there were trends towards decreased expression of NOS2, C1qa, and IL1a in 3-month old TREM2+/− vs. TREM2+/+ mice. Loss of a single copy of trem2 had no effect on Aβ pathology, but altered the morphological phenotype of plaque-associated microglia. These data suggest that TREM2 is important for the microglial response to Aβ deposition but that a 50% decrease inTREM2 expression does not affect Aβ plaque burden.
THE PRODUCTION OF AN EXOTOXIN BY CERTAIN STRAINS OF STAPHYLOCOCCUS AUREUS
Authors: Julia T. Parker
Journal: The Journal of Experimental Medicine (1924)

1. The sterile Berkefeld filtrates of broth cultures of certain strains of Staphylococcus aureus have a selective poisonous action for the skin of rabbits. 2. The poison is thermolabile, being completely destroyed when heated to 55 degrees C for 1 hour. 3. The poison when injected intradermally into rabbits stimulates the production of antitoxin. We therefore conclude that the poison is a soluble toxin.
The normal hip joint space: variations in width, shape, and architecture on 223 pelvic radiographs
Authors: M Lequesne, Jacques Malghem, E Dion
Journal: Annals of the Rheumatic Diseases (2004)

To determine the range of normal radiographic joint space width (JSW) values and the shape of the normal hip, and the influence of age, sex, dysplasia, coxa profunda, and acetabular roof curve abnormalities on these values.On routine conventional pelvic radiographs taken in the supine position in patients with no history of hip or lumbar pain, JSW was measured at three points (superolateral, apical, superomedial), together with the VCE, HTE, and neck shaft angles; acetabular depth; and femoral head diameter.223 radiographs (446 hips) from 127 women and 96 men (mean age 51.3 years) were examined. Interindividual variations in JSW were large (apical site: 4.19 (0.92) mm; range 2-7). Mean JSW values were higher at the superolateral site than at the apical and superomedial sites in nearly 80% of cases. Women had lower JSW values than men. JSW values did not fall with age. Marked right/left JSW asymmetry was seen in 13/221 (5.9%) subjects. Eight cases of acetabular dysplasia (7 unilateral) and 16 cases of coxa profunda were found, but no cases of acetabular protrusion. The JSW was thicker in dysplastic hips, and thinner in hips with coxa profunda. A roof curve abnormality was found in 96/446 (21.5%) hips.Normal JSW values vary widely; the JSW is commonly narrower at the superomedial site than at the apical site, and is sometimes asymmetric. The roof curve is dysmorphic in about 20% of patients. These findings may have important implications for epidemiological studies and early diagnosis of osteoarthritis of the hip.
Tobacco: Science, Policy and Public Health
Authors: Simon Chapman
Journal: BMJ (2005)

I n this digital age, when almost anything can be “Googled” and medical abstracts can be downloaded from PubMed to your desk in a nanosecond, why bother producing an 800 page doorstopper with syntheses of 44 topics written by the glitterati of the tobacco research and policy world? As we drown in information, such books can be liferafts of sanity. Aggregators and distillers of information at the peak of their fields do us all a service, as do those who have the patience to compile convenient collections like this one.

Eds Peter Boyle, Nigel Gray, Jack …
ACE Gene Polymorphism as a Prognostic Indicator in Patients With Type 2 Diabetes and Established Renal Disease
Authors: Stephen Fava, Joseph Azzopardi, Sian Ellard, Andrew T. Hattersley
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate whether the DD genotype is a predictor of mortality and of the decline in renal function in patients with type 2 diabetes and established nephropathy. RESEARCH DESIGN AND METHODS—A total of 56 such patients of Maltese Caucasian descent were recruited, and their ACE genotype was determined. Serum creatinine was estimated approximately every 4 months. The glomerular filtration rate (GFR) was calculated according to the Cockroft-Gault formula, and rate of change was determined by regression analysis. RESULTS—The rate of change in calculated GFR was −7.76 ml · min–1 · year–1 in those with the DD genotype (n = 31) and −1.17 ml · min–1 · h–1 in those with the ID or II genotype (n = 25) (P &amp;lt; 0.01). The 3-year mortality was 45.2% in the DD group compared with 20.0% in the ID/II group (P &amp;lt; 0.05). CONCLUSIONS—The DD genotype of the ACE gene polymorphism is associated with a more rapid decline in renal function and higher mortality in type 2 diabetic patients with established nephropathy.
Complete congruence between morphological and rbcL-based molecular phylogenies in birches and related species (Betulaceae).
Authors: J Bousquet, S H Strauss, P Li
Journal: Molecular Biology and Evolution (1992)

Estimations of phylogenies from morphological and molecular data often show contrasting results. We compared morphological and molecular phylogenies in an ancient family of woody dicots, the Betulaceae (birch family). The phylogeny of the family was estimated from parsimony analysis of morphological characters in the genera Alnus, Betula, Carpinus, Corylus, Ostrya, and Ostryopsis and from parsimony and distance-matrix analyses of DNA sequences of the chloroplast gene encoding the large subunit of ribulose-1,5-biphosphate carboxylase (rbcL) in the genera Alnus, Betula, Carpinus, Corylus, and Ostrya and in two outgroups, Quercus and Liquidambar. The topologies obtained by the different methods were completely congruent, and bootstrapping strongly supported the division of the family Betulaceae into two major clades, Betuleae (Alnus and Betula) and Coryleae (other members). Only slightly more homoplasy was present in the rbcL sequence data set than in the morphological set. Relative-rate tests indicated that the Coryleae clade had a faster rate of rbcL evolution than did the Betuleae clade. Heterogeneity of rates of morphological evolution also paralleled those for rbcL.
T‐helper 17 cytokines expression in leprosy skin lesions
Authors: J.A.S. Quaresma, T.L.S. Aarão, J.R. Sousa, B.S. Botelho, L.F. Barros, R.S. Araujo, J.L.P. Rodrigues, D.L. Prudente, D.S. Pinto, F.R.O. Carneiro, H.T. Fuzii
Journal: British Journal of Dermatology (2014)

Funding sources: Conselho Nacional de Pesquisa (CNPq), Brazil. Conflicts of interest: none declared. Dear Editor, Until recently, it was believed that T‐helper (Th) 1 and Th2 lymphocytes were the only effector cells of the immune response; however, another group of T cells producing cytokines that differ from those observed in the Th1–Th2 model has been identified recently. These cells comprise a third subtype of CD4+ effector T‐helper called type 17 Th cells, or Th17.1 Th17 lymphocytes produce interleukin (IL)‐17, IL‐17F, IL‐6, IL‐21, IL‐22 and tumour necrosis factor‐α, which play a role in both tissue inflammation and neutrophil activation.2 IL‐17 is a potent proinflammatory cytokine that exerts effects on a variety of cells.2 In leprosy, the cytokine profile of the tuberculoid and lepromatous forms (stable forms) has been extensively investigated and is characterized by a Th1 and Th2 response, respectively.3 However, the dimorphic forms are highly unstable and complex and Th17 lymphocytes may play an important role in the immunopathology of these lesions.
Thrombin-mediated release of lipids from pulmonary artery endothelial cells promotes neutrophil adherence.
Authors: M A Fisher, P J Del Vecchio, G P Palace, E M Denholm, L Lai, A B Malik
Journal: Circulation Research (1991)

We previously have described the ability of alpha-thrombin (the native procoagulant enzyme) to stimulate adherence of neutrophils to pulmonary artery endothelial cells. In the present study, we observed that conditioned medium factors released by alpha-thrombin (10(-8) M) treatment of cultured ovine pulmonary artery endothelial cells increased neutrophil adherence to naive pulmonary artery endothelial monolayers. This effect was independent of any residual alpha-thrombin present in the medium. In contrast to thrombin-induced neutrophil adherence, adherence of neutrophils mediated by the conditioned medium was not inhibited by the anti-CD18 monoclonal antibody 60.3, indicating a CD18-independent mechanism. The factors generated by the action of alpha-thrombin on endothelial cells also resulted in concentration-dependent neutrophil migration. The neutrophil adherence- and migration-promoting activities were isolated in the ether portion after extraction of the conditioned medium. Chromatographic analysis showed that the active components (which resolved into two peaks by reversed-phase high-performance liquid chromatography) were relatively hydrophilic low molecular weight lipids without phosphorus or amino acids. Reconstitution of these peaks indicated that they mediated neutrophil adhesion and migration responses. The results indicate that lipid factors promoting neutrophil adhesion and migration are generated by the action of thrombin on pulmonary artery endothelial cells. The generation of these factors may contribute to the amplification of the lung inflammatory response after pulmonary intravascular coagulation induced by thrombin.