tbuckley/cabot-search huggingface dataset:
MOLECULAR WEIGHT, ELECTROCHEMICAL AND BIOLOGICAL PROPERTIES OF TUBERCULIN PROTEIN AND POLYSACCHARIDE MOLECULES
Authors: Florence B. Seibert, Kai O. Pedersen, Arne Tiselius
Journal: The Journal of Experimental Medicine (1938)

Studies have been made by means of sedimentation in the ultracentrifuge, and by diffusion and electrophoresis, to determine the molecular weights and homogeneity of the tuberculin protein and polysaccharide molecules as found in their natural state in the unchanged filtrates from culture media after growth of tubercle bacilli. These results have been compared with data obtained on fractions isolated by chemical procedures from them or from old tuberculin. By means of electrophoresis in the Tiselius apparatus it was possible to separate the protein from the polysaccharide, as these two fractions occur naturally in the original culture medium filtrates of acid-fast bacilli. The protein from the bovine strain of bacillus proved to be homogeneous in sedimentation (S(20) = 1.6), diffusion (D(20) = 12.0) and electrophoresis, with a molecular weight of about 10,000. The tuberculin polysaccharide isolated in electrophoresis appeared to be practically the same in sedimentation and in precipitin reaction as the polysaccharide isolated by chemical procedure. The latter proved to be homogeneous in sedimentation (S(20) = 1.6) and diffusion (D(20) = 11.0) with a molecular weight of about 9000. A practically homogeneous protein was isolated from the culture filtrate of the human tubercle bacillus H 37 by fractional ammonium sulfate precipitation, with a molecular weight of 32,000 (S(20) = 3.3; D(20) = 8.2). It was electrochemically homogeneous, with an isoelectric point at pH 4.3 and an isoionic point at pH 4.7. It could be dried or frozen with no loss in homogeneity. It was highly antigenic in the precipitin reaction and produced the anaphylactic type of local skin reaction in tuberculous guinea pigs, in contrast to the true tuberculin type of reaction caused by a purified PPD fraction. Furthermore death resulted in tuberculous guinea pigs from intracutaneous injection of exceptionally small amounts. A protein with molecular weight of about 17,000 was isolated from the filtrate from cultures of the timothy bacillus. The nucleic acid originally occurring in old tuberculin (OT) seems to be responsible for the high electrochemical mobility observed. From OT and the PPD made from it, potent but non-antigenic molecules of 16,000 and 9000 weight and with a low content of nucleic acid were isolated. With increase in size these deviated much from the normal compact spherical shape, and aggregation was evident from the tendency toward gel formation. The smallest molecule (9000) was homogeneous (S(20) = 1.0; D(20) = 10.0) and had lost some tuberculin potency.
Measurement of PO2 and PCO2 of gases and liquids at 2Ata using externally pressurized electrodes
Authors: J. P. BLACKBURN, H. CONNOR, F. M. DAVIS, T. W. GREENWOOD, P. MARKS, H. F. SEELEY
Journal: Cardiovascular Research (1975)

A system has been developed to measure the PO2 and PCO2 of gases and liquids under hyperbaric conditions for use with a pure oxygen, 'single patient' hyperbaric chamber (Vickers Medical Ltd). The measuring equipment is mounted outside the chamber.

Conventional electrodes are used for the measurement of PO2 and PCO2 (Radiometer E5046, E5036), they are mounted in stainless steel cuvettes and used in conjunction with a digital pH meter (Radiometer PHM72). The cuvettes are maintained at 2Ata, but the rest of each electrode is at ambient pressure. Blood, saline, or gas samples from a specially designed tonometer can be introduced into the cuvettes under hyperbaric conditions.

Linearity and reproducibility of oxygen were checked over the range 1100–1400 mm Hg (146–186 kPa) using gas mixtures. The means of a series of determinations for each mixture were within 4 mm Hg (0.53 kPa) of a line based on a two-point calibration using white spot nitrogen and 100% oxygen. For each mixture the standard deviation never exceeded 5.1 mm Hg (0.68 kPa).

A gas-liquid difference exists under hyperbaric conditions which is about 5% for saline, 9% for blood, and 12% for 30% glycerol.

The PCO2 of gas mixtures in the range 20–85 mm Hg (2.7–11.3 kPa) can be measured to within ± 1 mm Hg (0.13 kPa) of the values calculated from Haldane analysis. A gas-liquid difference for CO2 also exists under hyperbaric conditions, the liquid reading about 8% higher than gas of the same PCO2. This difference has not been explained, and is not found when the same system is used under normobaric conditions.

The equipment is now being used for clinical studies.
The dopamine hypothesis of schizophrenia: focus on the dopamine receptor
Authors: Solomon H. Snyder
Journal: American Journal of Psychiatry (1976)

Alleviation of schizophrenic symptoms by phenothiazines and butyrophenones is associated with blockade of dopamine receptors, while exacerbation of symptoms by amphetamines appears to result from enhanced synaptic activity of dopamine and/or norepinephrine. The author suggests that biochemical labeling of the dopamine receptor with 3H-dopamine and 3H-haloperidol may clarify mechanisms of drug effects on the dopamine receptor.
Antigen Presentation by Dendritic Cells in Tumors Is Disrupted by Altered Metabolism that Involves Pyruvate Kinase M2 and Its Interaction with SOCS3
Authors: Zhuohan Zhang, Qiaofei Liu, Yongzhe Che, Xin Yuan, Lingyun Dai, Bin Zeng, Guohui Jiao, Yin Zhang, Xue Wu, Yinyan Yu, Yuan Zhang, Rongcun Yang
Journal: Cancer Research (2009)

Dendritic cell (DC) function is negatively affected by tumors and tumor-derived factors, but little is known about the underlying mechanisms. Here, we show that intracellular SOCS3 in DCs binds to pyruvate kinase type M2 (M2-PK), which plays a critical role in ATP production through glycolysis. The interaction of SOCS3 with M2-PK reduced ATP production and impaired DC-based immunotherapy against tumors. Thus, SOCS3, which has been shown to be upregulated by tumor-derived factors, interacts with M2-PK to decrease ATP production, causing DC dysfunction. These dysfunctional DCs have a reduced ability to present antigens. Alteration of DC metabolism mediated by SOCS3 represents a novel mechanism for DC dysfunction in the tumor microenvironment.
Critical Time Window for Intra-Arrest Cooling With Cold Saline Flush in a Dog Model of Cardiopulmonary Resuscitation
Authors: Ala Nozari, Peter Safar, S. William Stezoski, Xianren Wu, Scott Kostelnik, Ann Radovsky, Samuel Tisherman, Patrick M. Kochanek
Journal: Circulation (2006)

Background— Mild hypothermia improves outcome when induced after cardiac arrest in humans. Recent studies in both dogs and mice suggest that induction of mild hypothermia during cardiopulmonary resuscitation (CPR) greatly enhances its efficacy. In this study, we evaluate the time window for the beneficial effect of intra-arrest cooling in the setting of prolonged CPR in a clinically relevant large-animal model. Methods and Results— Seventeen dogs had ventricular fibrillation cardiac arrest no flow of 3 minutes, followed by 7 minutes of CPR basic life support and 50 minutes of advanced life support. In the early hypothermia group (n=9), mild hypothermia (34°C) was induced with an intravenous fluid bolus flush and venovenous blood shunt cooling after 10 minutes of ventricular fibrillation. In the delayed hypothermia group (n=8), hypothermia was induced at ventricular fibrillation 20 minutes. After 60 minutes of ventricular fibrillation, restoration of spontaneous circulation was achieved with cardiopulmonary bypass for 4 hours, and intensive care was given for 96 hours. In the early hypothermia group, 7 of 9 dogs survived to 96 hours, 5 with good neurological outcome. In contrast, 7 of 8 dogs in the delayed hypothermia group died within 37 hours with multiple organ failure ( P =0.012). Conclusions— Early application of mild hypothermia with cold saline during prolonged CPR enables intact survival. Delay in the induction of mild hypothermia in this setting markedly reduces its efficacy. Our data suggest that if mild hypothermia is used during CPR, it should be applied as early as possible.
Beneficial effects of PPAR-? ligands in ischemia?reperfusion injury, inflammation and shock
Authors: M ABDELRAHMAN, A SIVARAJAH, C THIEMERMANN
Journal: Cardiovascular Research (2005)

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR-γ regulates gene expression by forming a heterodimer with the retinoid X receptor (RXR) before binding to sequence-specific PPAR response elements (PPREs) in the promoter region of target genes, thereby regulating several metabolic pathways, including lipid biosynthesis and glucose metabolism. Thiazolidinediones (TZDs, i.e. rosiglitazone, pioglitazone), which are synthetic PPAR-γ agonists, act as insulin sensitizers and are used in the treatment of type 2 diabetes. In the last few years, it has, however, become evident that the therapeutic effects of PPAR-γ ligands reach far beyond their use as insulin sensitizers. Recently, PPAR-γ has been implicated as a regulator of cellular inflammatory and ischemic responses. PPAR-γ agonists may exert their anti-inflammatory effects by negatively regulating the expression of pro-inflammatory genes induced during macrophage differentiation and activation, by either PPAR-γ-dependent or -independent mechanisms. Several lines of evidence suggest that TZDs protect the heart and other organs against the tissue injury caused by ischemia/reperfusion (I/R) injury and shock. This review discusses the anti-inflammatory signalling pathways activated by PPAR-γ, as well as the potential therapeutic effects of PPAR-γ agonists in animal models of ischemia/reperfusion, inflammation and shock.
Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.
Authors: D J Rader, K Ikewaki, N Duverger, H Schmidt, H Pritchard, J Frohlich, M Clerc, M F Dumon, T Fairwell, L Zech
Journal: Journal of Clinical Investigation (1994)

Classic (complete) lecithin:cholesterol acyltransferase (LCAT) deficiency and Fish-eye disease (partial LCAT deficiency) are genetic syndromes associated with markedly decreased plasma levels of high density lipoprotein (HDL) cholesterol but not with an increased risk of atherosclerotic cardiovascular disease. We investigated the metabolism of the HDL apolipoproteins (apo) apoA-I and apoA-II in a total of five patients with LCAT deficiency, one with classic LCAT deficiency and four with Fish-eye disease. Plasma levels of apoA-II were decreased to a proportionately greater extent (23% of normal) than apoA-I (30% of normal). In addition, plasma concentrations of HDL particles containing both apoA-I and apoA-II (LpA-I:A-II) were much lower (18% of normal) than those of particles containing only apoA-I (LpA-I) (51% of normal). The metabolic basis for the low levels of apoA-II and LpA-I:A-II was investigated in all five patients using both exogenous radiotracer and endogenous stable isotope labeling techniques. The mean plasma residence time of apoA-I was decreased at 2.08 +/- 0.27 d (controls 4.74 +/- 0.65 days); however, the residence time of apoA-II was even shorter at 1.66 +/- 0.24 d (controls 5.25 +/- 0.61 d). In addition, the catabolism of apoA-I in LpA-I:A-II was substantially faster than that of apoA-I in LpA-I. In summary, genetic syndromes of either complete or partial LCAT deficiency result in low levels of HDL through preferential hypercatabolism of apoA-II and HDL particles containing apoA-II. Because LpA-I has been proposed to be more protective than LpA-I:A-II against atherosclerosis, this selective effect on the metabolism of LpA-I:A-II may provide a potential explanation why patients with classic LCAT deficiency and Fish-eye disease are not at increased risk for premature atherosclerosis despite markedly decreased levels of HDL cholesterol and apoA-I.
Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy
Authors: Dinesh Selvarajah, Rajiv Gandhi, Celia J. Emery, Solomon Tesfaye
Journal: Diabetes Care (2009)

OBJECTIVE To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. RESULTS There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. CONCLUSIONS This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN.
SOME OBSERVATIONS ON THE CAUSATION OF ERYTHEMA EXUDATIVUM MULTIEORME (HEBRA)
Authors: EDWIN RAMEL
Journal: British Journal of Dermatology (1930)

Journal Article SOME OBSERVATIONS ON THE CAUSATION OF ERYTHEMA EXUDATIVUM MULTIEORME (HEBRA) Get access EDWIN RAMEL EDWIN RAMEL Lausanne, Switzerland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 42, Issue 1, 1 January 1930, Pages 1–25, https://doi.org/10.1111/j.1365-2133.1930.tb14358.x Published: 01 January 1930
Relationship between the physical size, incompetence, and stenosis of prosthetic mitral valves
Authors: J. T. M. Wright, L. J. Temple
Journal: Thorax (1972)

One each of 17 commercially available prosthetic mitral valves has been subjected to <i>in vitro</i> testing using a pulse duplicator. Measurements of mean diastolic pressure difference, incompetence, dimensions, mechanical movements, and turbulence were made, and the quality of manufacture was examined. Although most valves would be effective in the treatment of incompetence, only those with large orifice diameters produced no significant stenosis. All the valves tested were in clinical use at some time in the period 1966-71. Most of the prostheses were obtained in 1968 or 1969. Many of this group showed a manufacturing standard which was less than impeccable.
Response to Letter Regarding Article, “Peripheral Nociception Associated With Surgical Incision Elicits Remote Nonischemic Cardioprotection via Neurogenic Activation of Protein Kinase C Signaling”
Authors: W. Keith Jones, Guo-Chang Fan, Siyun Liao, Evangelia G. Kranias, Jo El Schultz, Xiaoping Ren, Jun-Ming Zhang, John Lorenz, Yang Wang, Neal L. Weintraub
Journal: Circulation (2010)
Treatment With Autologous Antigen-Presenting Cells Activated With the HER-2 –Based Antigen Lapuleucel-T: Results of a Phase I Study in Immunologic and Clinical Activity in HER-2–Overexpressing Breast Cancer
Authors: John W. Park, Michelle E. Melisko, Laura J. Esserman, Lori A. Jones, Jami Breen Wollan, Robert Sims
Journal: Journal of Clinical Oncology (2007)

Lapuleucel-T (APC8024), an autologous active cellular immunotherapy, was prepared from peripheral-blood mononuclear cells, including antigen-presenting cells, that were activated in vitro with recombinant fusion protein BA7072. This antigen construct consisted of sequences from intracellular and extracellular domains of human epidermal growth factor receptor 2 (HER-2) linked to granulocyte-macrophage colony-stimulating factor. We conducted a phase I study to evaluate the safety and immunologic activity of lapuleucel-T in patients with HER-2-overexpressing metastatic breast cancer.Metastatic breast cancer patients whose tumors overexpressed or amplified HER-2 were eligible. Patients underwent leukapheresis and subsequent lapuleucel-T infusion 2 days later at weeks 0, 2, and 4. Patients who achieved a partial response (PR) or had stable disease (SD) lasting through week 48 were eligible for re-treatment using the same protocol and dose as their initial treatment. End points included safety, immunologic activity, and antitumor activity.Nineteen patients were enrolled; 18 patients received treatment. Therapy was well tolerated, with no grade 3 or 4 adverse events associated with the treatment. Significant cellular immune responses specific for the immunizing antigen and HER-2 sequences were induced after treatment, as measured by lymphocyte proliferation and interferon gamma enzyme-linked immunospot assay. One patient experienced a PR lasting 6 months. Three additional patients had SD lasting more than 1 year.Autologous active cellular immunotherapy with lapuleucel-T was feasible, safe, and well tolerated. The treatment stimulated significant immune responses, which were enhanced after boost infusions. Lapuleucel-T therapy was associated with tumor response or extended disease stabilization in some patients and warrants further investigation.
Evidence of Selection on the Domesticated ERVWE1 env Retroviral Element Involved in Placentation
Authors: B. Bonnaud
Journal: Molecular Biology and Evolution (2004)

The human endogenous retrovirus HERV-W multicopy family includes a unique proviral locus, termed ERVWE1, which contains gag and pol pseudogenes and has retained a full-length envelope open reading frame (ORF). This Env protein (syncytin) is a highly fusogenic membrane glycoprotein and has been proposed to be involved in hominoid placental physiology. To track the hallmarks of natural selection acting on the ERVWE1 env gene, the pattern of substitutions and indels was analyzed within all human HERV-W elements and along the ERVWE1 orthologous loci in chimpanzee, gorilla, orangutan, and gibbon. The comparison of ERVWE1 and paralogous HERV-W copies revealed an ERVWE1-specific signature consisting of a four amino acid deletion in the intracytoplasmic tail of the glycoprotein. We show that this deletion is crucial for the envelope fusogenic activity. The comparison of the human ERVWE1 locus with its orthologs demonstrates the existence of a selective pressure to maintain the env reading frame open. Notably, the 3′ part of the env gene, encoding regions required for the fusion process, is under purifying selection. The identification of selective constraints on env ERVWE1 confirms that this retroviral locus has been recruited in the hominoid lineage to become a bona fide gene.
Risk Factors for Silent Myocardial Ischemia in High-Risk Type 1 Diabetic Patients
Authors: Ariane Sultan, Christophe Piot, Denis Mariano-Goulart, Manase Rasamisoa, Eric Renard, Antoine Avignon
Journal: Diabetes Care (2004)

Coronary artery disease (CAD) is the leading cause of mortality in people with type 1 diabetes. Silent myocardial ischemia (SMI) is common in this population (1), and a large body of evidence attests to the high diagnostic yield of stress myocardial perfusion imaging (MPI) for the prediction of major coronary events (2,3). However, screening all patients with stress MPI is not practical and should be limited to those with a high-risk profile (4). No such profile has been determined in type 1 diabetic patients.

We thus evaluated the clinical and biological variables associated with silent coronary stenosis to determine a high-risk profile of asymptomatic type 1 diabetic patients who should benefit from stress MPI screening.

All asymptomatic type 1 diabetic patients admitted to our department between January 1999 and June 2002 were considered for SMI screening, using dipyridamol (0.75 mg/kg) combined with exercise on an ergometer bicycle (when feasible) and stress-gated single-photon emission computed tomographic99Tcm-MIBI imaging if they had at least one of the following conditions: one other major cardiovascular risk factors, age ≥60 years, or peripheral arterial disease (PAD). Patients with known CAD, age ≥80 or <30 years, and dipyridamole contraindications were excluded. Participants were considered to have type 1 diabetes if they had a history of ketosis and started insulin treatment in the 2 …
BLOOD AND BONE MARROW CELLS OF THE DOMESTIC FOWL
Authors: Claude E. Forkner
Journal: The Journal of Experimental Medicine (1929)

1. A simple, direct method of counting leucocytes of the fowl is described. 2. Twenty-nine complete, morphological studies of the blood of eleven domestic fowls are recorded. 3. The characteristics of the cells found in the blood and bone marrow are described in detail and their relative numbers reported. 4. The supravital technique, using neutral red and Janus green, enables one to separate and classify accurately the confusing cells of the blood and bone marrow. 5. These studies provide a basis for future experimental studies on the blood and bone marrow cells of the fowl.
Stent-Based Delivery of Sirolimus Reduces Neointimal Formation in a Porcine Coronary Model
Authors: Takeshi Suzuki, Greg Kopia, Shin-ichiro Hayashi, Lynn R. Bailey, Gerard Llanos, Robert Wilensky, Bruce D. Klugherz, George Papandreou, Pallassana Narayan, Martin B. Leon, Alan C. Yeung, Fermin Tio, Philip S. Tsao, Robert Falotico, Andrew J. Carter
Journal: Circulation (2001)

The purpose of this study was to determine the efficacy of stent-based delivery of sirolimus (SRL) alone or in combination with dexamethasone (DEX) to reduce in-stent neointimal hyperplasia. SRL is a potent immunosuppressive agent that inhibits SMC proliferation by blocking cell cycle progression.Stents were coated with a nonerodable polymer containing 185 microgram SRL, 350 microgram DEX, or 185 microgram SRL and 350 microgram DEX. Polymer biocompatibility studies in the porcine and canine models showed acceptable tissue response at 60 days. Forty-seven stents (metal, n=13; SRL, n=13; DEX, n=13; SRL and DEX, n=8) were implanted in the coronary arteries of 16 pigs. The tissue level of SRL was 97+/-13 ng/artery, with a stent content of 71+/-10 microgram at 3 days. At 7 days, proliferating cell nuclear antigen and retinoblastoma protein expression were reduced 60% and 50%, respectively, by the SRL stents. After 28 days, the mean neointimal area was 2.47+/-1.04 mm(2) for the SRL alone and 2.42+/-1.04 mm(2) for the combination of SRL and DEX compared with the metal (5.06+/-1.88 mm(2), P<0.0001) or DEX-coated stents (4.31+/-3.21 mm(2), P<0.001), resulting in a 50% reduction of percent in-stent stenosis.Stent-based delivery of SRL via a nonerodable polymer matrix is feasible and effectively reduces in-stent neointimal hyperplasia by inhibiting cellular proliferation.
Type 2 Diabetes Prevalence in Asian Subjects
Authors: Marguerite J. McNeely, Edward J. Boyko
Journal: Diabetes Care (2004)

We thank Sone et al. (1) for their letter in response to our article (2) on the prevalence of type 2 diabetes in Asian Americans. Dr. Sone raises some interesting points that highlight the need for more studies of type 2 diabetes in Asian populations.

We did …