gebhart/patrepeval huggingface dataset:
Development of an attenuated strain for Japanese encephalitis live virus vaccine for porcine use. (1975)

To develop Japanese encephalitis live virus vaccine for the prevention of stillbirth in swine, an attempt was made to produce an attenuated virus. Primary bovine kidney cell culture was used to carry out serial passages of a field strain at 30 degrees C for a long time. During these passages cloning was repeated with the character of reproductive capacity at given temperature (rct) and plaque sizes as markers. As a result, an attenuated S- strain was produced successfully. It was rct/37- and rct/40- and formed small-sized plaques. In this strain a marked attenuation was seen in peripheral infectivity to suckling mice and in intracerebral infectivity to adult mice. When inoculated with this strain, newborn piglets manifested no abnormal clinical signs or pathological changes of the brain tissue at all. A minute amount of virus was rarely recovered from some lymph nodes and blood. Little virus was recovered from various organs. No viremia was detected from any piglet more than one month of age inoculated with recovered virus. No infection of the placenta or fetus was recognized in any pregnant sow inoculated with recovered virus. Inoculated sows gave birth to normal young. Furthermore, when mosquitoes of Culex tritaeniorhynchus summorosus were allowed to suck infected blood by the membrane feeding technique, the virus recovered from them showed an infectivity more reduced than the field strain. From these results, it was presumed that the S- strain might be safe enough to be used as live virus vaccine for swine.
The Pathology of Uterine Smooth Muscle Tumors and Mixed Endometrial Stromal-Smooth Muscle Tumors: A Selective Review with Emphasis on Recent Advances (2000)

This review focuses on the pathology of uterine smooth muscle tumors (SMTs), with a particular emphasis on those studies published in the past 15 years that have expanded our knowledge of these tumors which still present diagnostic challenges for the pathologist. Leiomyoma variants, leiomyosarcoma, SMTs of low or uncertain malignant potential, epithelioid SMTs, SMTs with unusual growth patterns, and mixed endometrial stromal-SMTs are discussed.
Electrocatalytic CO 2 Conversion to Oxalate by a Copper Complex (2010)

Global warming concern has dramatically increased interest in using CO2 as a feedstock for preparation of value-added compounds, thereby helping to reduce its atmospheric concentration. Here, we describe a dinuclear copper(I) complex that is oxidized in air by CO2 rather than O2; the product is a tetranuclear copper(II) complex containing two bridging CO2-derived oxalate groups. Treatment of the copper(II) oxalate complex in acetonitrile with a soluble lithium salt results in quantitative precipitation of lithium oxalate. The copper(II) complex can then be nearly quantitatively electrochemically reduced at a relatively accessible potential, regenerating the initial dinuclear copper(I) compound. Preliminary results demonstrate six turnovers (producing 12 equivalents of oxalate) during 7 hours of catalysis at an applied potential of -0.03 volts versus the normal hydrogen electrode.
Identification of residues in GTPase-activating protein Src homology 2 domains that control binding to tyrosine phosphorylated growth factor receptors and p62 (1992)

Ras GTPase-activating protein (GAP) contains two Src homology 2 (SH2) domains which are implicated in binding to tyrosine-phosphorylated sites in specific activated growth factor receptors and to a cytoplasmic tyrosine-phosphorylated protein, p62. We have used site-directed mutagenesis of the two GAP SH2 domains (SH2-N and SH2-C) to identify residues involved in receptor and p62 binding. A bacterial fusion protein containing the precise SH2-N domain, as defined by sequence homology, associated with both the activated beta platelet-derived growth factor receptor and epidermal growth factor receptor, and p62 in vitro. However, short deletions at either the N or C termini of the SH2-N domain abolished binding, suggesting that the entire SH2 sequence is required for formation of an active domain. Conservative substitutions of 2 highly conserved basic residues in the SH2-N domain, an arginine and a histidine, resulted in complete loss of receptor and p62 binding, whereas other basic residues, and residues at variable SH2 sites, were more tolerant of substitution. The conserved arginine and histidine therefore appear critical for association with phosphotyrosine-containing proteins, possibly through an interaction with phosphotyrosine. The GAP SH2-C domain, unlike SH2-N, does not bind efficiently to activated receptors or p62 in vitro. The SH2-C domain lacks 3 residues which are otherwise well conserved, and contribute to high affinity SH2-N binding. Replacement of 1 of these residues, a cysteine, with the consensus glycine, conferred SH2-C binding activity toward tyrosine-phosphorylated p62 and epidermal growth factor receptor. Loss-of-function and gain-of-function mutations in the GAP SH2 domains can therefore be used to identify residues that are critical for receptor and p62 binding.
Modifications of the iron–neuromelanin system in Parkinson's disease (2006)

Parkinson's disease is a common neurodegenerative disorder with a mainly sporadic aetiology, although a number of monogenic familiar forms are known. Most of the motor symptoms are due to selective depletion of dopaminergic, neuromelanin-containing neurones of the substantia nigra pars compacta. Neuromelanin is the dark insoluble macromolecule that confers the black (substantia nigra) or grey (locus coeruleus) colour to monoaminergic basal ganglia. In particular, nigral neurones are pigmented because of the accumulation of by-products of oxidative metabolism of the neurotransmitter dopamine. The occurrence of dopamine (and all the enzymatic machinery required for dopamine synthesis, re-uptake and disposal) and neuromelanin, and a large amount of iron ions that interact with them, makes dopaminergic nigral neurones peculiarly susceptible to oxidative stress conditions that, in turn, may become amplified by the iron-neuromelanin system itself. In this mini-review we describe biophysical evidence for iron-neuromelanin modifications that support this hypothesis. Furthermore, we discuss the formation of the covalent linkage between alpha-synuclein and neuromelanin from the early stages of the disease.
Conformational Studies and Electronic Structures of Tamoxifen and Toremifene and Their Allylic Carbocations Proposed as Reactive Intermediates Leading to DNA Adduct Formation (1996)

Toremifene, a compound which differs from tamoxifen by the substitution of a chlorine atom for a hydrogen atom in the ethyl group, is significantly less potent than tamoxifen in causing DNA adduct formation in rats. To examine the relationship of the DNA adduct-forming ability of these compounds with their physicochemical properties such as stable conformation and chemical reactivity, we carried out molecular mechanics, molecular dynamics, and quantum mechanics calculations for the two compounds. For tamoxifen, six stable conformers were identified by conformational search with CFF91 force field. Molecular dynamics simulations showed that these were often interconverted within 1.0 ns. On the other hand, although the conformation of stable conformers and dynamical behavior of toremifene were almost the same as those of tamoxifen, a few conformations were slightly different from those of tamoxifen owing to the effect of the chlorine atom at chloroethyl group. In addition, the stability of the allylic carbocation, which had been proposed as the reactive intermediate leading to DNA adduct formation, was calculated with both semiempirical and density functional methods. Results showed that the carbocation intermediate of toremifene was less stable than that of tamoxifen by 4-5 kcal/mol, suggesting that toremifene was less frequently activated to the intermediate than tamoxifen. Furthermore, the carbocation intermediates of two other tamoxifen derivatives, 4-iodotamoxifen and droxifene, which show no DNA adduct-forming ability, were also less stable compared with that of tamoxifen. These calculated results suggest a close relation between the stability of the proposed carbocation intermediate and DNA adduct-forming ability.
Principles of Pharmacology: Basic Concepts and Clinical Applications (1996)

Part 1 General principles: Pharmacodynamics - drug receptors and receptor mechanisms Pharmacokinetics - disposition and metabolism of drugs Drug development, the evaluation of new drugs and principles of therapeutics. Part 2 Peripheral neuropharmacology: Chemical neurotransmission, peripheral autonomic nervous system Pharmacology of cholingeric transmission Pharmacology of the sympathetic nervous system Neuromuscular transmission - agonists, antagonists Pharmacology of the adrenal medulla Autacoids in peripheral autonomic pharmacology Local anesthetics Uterine pharmacology. Part 3 Central neuropharmacology: Relationships of drugs acting in the nervous system neurotransmission General anesthetic drugs Drugs used for the treatment of anxiety and sleep disorders General principles of drug therapy in psychiatric disorders Antipsychotic agents Drugs used for the treatment of affective disorders Drugs used for the treatment of neurological disorders Epilepsy and anticonvulsants Opioid analgesics and antagonists Drug abuse and addiction, including alcohol CNS stimulants. Part 4 Cardiovascular and pulmonary pharmacology. Cardiovascular pharmacology: Agents used in the management of heart failure Antischemic drugs Antiarrhythmic drugs Antihypertensive drugs Specific vascular disorders Monitoring of cardiovascular and pulmonary drugs and treatment of their intoxications. Pulmonary pharmacology: Bronchodilators Anti-inflamatory management of bronchospastic disease Cromalyn sodium, nedocrimil sodium and related compounds Repiratory stimulants Antitussive agents Drugs acting on mucociliary transport surface. Part 5 Renal pharmacology: Introduction Fluid and electrolyte balance General principles and renal mechanisms of drug transport Diuretics Antidiuretic hormone, synthetic analogs and related agents Drug-induced kidney disease. Part 6 Pharmacology of hormones and reproduction: Insulin, glucagon and oral hypoglycemic agents in the treatment of diebetes mellitus Parathyroid hormone and diphosphonates Calcitonin Adrenal corticosteroids, adrenocorticotrophic hormone (ACTH), Corticotropin releasing hormone and antidrenal drugs Thyroid hormones, thyroid stimulating hormone (TSH), TSH-releasing hormone (TRH) and antithyroid drugs Estrogens Antiestrogens Progestins Contraceptive agents Androgenic and anabolic steroids and antagonists Gonadotropins Antiprogestins Activins and inhibins LHRH analog agonists and antagonists Growth hormone and insulin-like growth factors Prolactin and treatment of hyperprolactinemic states with bromocriptine. Part 7 Pharmacology of nutrients: Introduction to pharmacology of nutrients - nutritional requirements. Vitamins: Water-soluable vitamins - thiamin, riboflavin, niacin, pantothenate, pyridoxine, biotin, B12, folate and ascorbic acid Fat-soluable vitamins - vitamins A, D, E and K.
Lactate stimulates endothelial cell migration (2006)

The significance of the high lactate levels that characterize healing wounds is not fully understood. Lactate has been shown to enhance collagen synthesis by fibroblasts and vascular endothelial growth factor (VEGF) production by macrophages and endothelial cells. VEGF has been shown to induce endothelial cell migration. However, it has not been shown whether accumulated lactate correlates with the biological activity of VEGF. Therefore, we investigated the effect of lactate on migration of endothelial cells. Human umbilical vein endothelial cells and human microvascular endothelial cells were cultured to subconfluent monolayers in standard six-well tissue culture plates. Following a 24-hour serum starvation, cells were treated with the indicated concentrations of l-lactate. Cell migration was assessed using a modified Boyden chamber. VEGF protein in the cell culture supernatant was measured by enzyme-linked immunoassay. Lactate-enhanced VEGF protein synthesis in a time- and dose-dependent manner. Lactate added into the bottom well did not stimulate cellular migration from the upper well. However, lactate when added together with endothelial cells to the bottom well of the Boyden chamber increased cellular migration in a dose-dependent manner. This effect was blocked by anti-VEGF and by cycloheximide. Lactate enhances VEGF production in endothelial cells, although lactate, itself, is not a chemoattractant. We conclude that the lactate-mediated increase in cellular migration is regulated by VEGF.
Renal expression of osteopontin and alkaline phosphatase correlates with BUN levels in aged rats (1995)

Renal expression of alkaline phosphatase (AP) and osteopontin (OP) in rats of different age was examined. Northern blot hybridization showed that AP mRNA was reduced moderately, whereas OP mRNA was stimulated drastically in old rats. Dot-blot quantitation analysis showed that AP mRNA decreased 30% in 24-compared with 6-mo-old rats. In contrast, OP mRNA increased 3.1- and 9.1-fold, respectively, in 12- and 24-mo-old rats. beta-Actin mRNA did not change with age. Blood urea nitrogen (BUN) increased 47 and 187% in 12- and 24-mo-old rats, respectively. Correlation analysis showed that BUN correlated negatively with AP mRNA and positively with OP mRNA. No correlation was observed with beta-actin. The expression of these markers was also examined in femurs. AP and OP mRNAs were marginally reduced in old bones. To test whether the correlation also exists in other types of renal insufficiency, we examined these parameters in young rats infused with parathyroid hormone (PTH). BUN was elevated 3.5-fold, whereas AP mRNA decreased 48%, and OP mRNA increased 15.3-fold in kidneys of PTH-treated rats. To elucidate the possible mechanisms that lead to the overexpression of OP in kidney, we examined the expression of transforming growth factor-beta 1 (TGF-beta 1) mRNA. No significant differences in TGF-beta 1 expression were observed between young and old rats and control and PTH-treated young rats. Changes in the expression of OP were also visualized by immunostaining of renal sections. Alterations in the levels of OP and AP were validated by Western blot analysis and enzyme assay of homogenate, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Fibroblast Growth Factor Receptor Signaling Crosstalk in Skeletogenesis (2010)

Fibroblast growth factors (FGFs) play important roles in the control of embryonic and postnatal skeletal development by activating signaling through FGF receptors (FGFRs). Germline gain-of-function mutations in FGFR constitutively activate FGFR signaling, causing chondrocyte and osteoblast dysfunctions that result in skeletal dysplasias. Crosstalk between the FGFR pathway and other signaling cascades controls skeletal precursor cell differentiation. Genetic analyses revealed that the interplay of WNT and FGFR1 determines the fate and differentiation of mesenchymal stem cells during mouse craniofacial skeletogenesis. Additionally, interactions between FGFR signaling and other receptor tyrosine kinase networks, such as those mediated by the epidermal growth factor receptor and platelet-derived growth factor receptor α, were associated with excessive osteoblast differentiation and bone formation in the human skeletal dysplasia called craniosynostosis, which is a disorder of skull development. We review the roles of FGFR signaling and its crosstalk with other pathways in controlling skeletal cell fate and discuss how this crosstalk could be pharmacologically targeted to correct the abnormal cell phenotype in skeletal dysplasias caused by aberrant FGFR signaling.
Detection of human cytomegalovirus in plasma of AIDS patients during acute visceral disease by DNA amplification (1992)

By using the polymerase chain reaction (PCR) amplification procedure, 19 (83%) of 23 plasma specimens obtained from individuals with AIDS and human cytomegalovirus (HCMV) visceral disease were found to be positive for plasma viremia as detected by PCR (PV-PCR), whereas 78% of cultures of peripheral blood leukocytes from the same samples were found to be positive. All 11 specimens prospectively obtained from individuals with acute HCMV disease were positive by PV-PCR. Plasma specimens from patients who received ganciclovir therapy rapidly became both culture and PV-PCR negative, and there was an excellent correlation between the two procedures. DNA detected by PV-PCR was unaffected by filtering plasma through a 0.2-microns-pore-size filter, although a conserved cellular gene, HLA-DQ alpha, was undetectable by PCR following filtration. HCMV DNA in plasma could be quantitated by PV-PCR by using endpoint serial dilutions, with detectable virus being present in 10(1) to 10(-2) microliters of plasma. A low titer of infectious virus could be detected in 2 of 11 plasma samples. The detection of HCMV DNA in plasma by PV-PCR promises to be a useful procedure for monitoring patients with AIDS suspected of having impending, acute, or recurrent HCMV visceral disease and suggests an additional route by which virus may disseminate in the immunocompromised host.
Bright Light Induction of Strong (Type 0) Resetting of the Human Circadian Pacemaker (1989)

The response of the human circadian pacemaker to light was measured in 45 resetting trials. Each trial consisted of an initial endogenous circadian phase assessment, a three-cycle stimulus which included 5 hours of bright light per cycle, and a final phase assessment. The stimulus induced strong (type 0) resetting, with responses highly dependent on the initial circadian phase of light exposure. The magnitude and direction of the phase shifts were modulated by the timing of exposure to ordinary room light, previously thought to be undetectable by the human pacemaker. The data indicate that the sensitivity of the human circadian pacemaker to light is far greater than previously recognized and have important implications for the therapeutic use of light in the management of disorders of circadian regulation.
The Role of Glycosylation in Autoimmune Disease (1998)

Oligosaccharide structures play a key role in the antigenicity of a number of clinically important antigens such as blood group determinants. Interest in glycobiology has increased dramatically amongst immunologists during the last few years due to the fact that oligosaccharides also play a central role in adhesion and homing events during inflammatory processes (1), comprise powerful xenotransplantation antigens (2), and may provide targets for tumor immunotherapy (3). Additionally, alterations in glycosylation are now known to occur in a number of autoimmune diseases. This review will first discuss some general aspects of protein glycosylation and then explore some of the autoimmune diseases in which the role of glycosylation has been examined.
Cyclical mastalgia--is it a manifestation of aberration in lipid metabolism? (1994)

Several therapeutic and investigative studies suggest the possibility of the role of lipid profile aberrations in the pathophysiology of cyclical mastalgia. This prospective study is aimed to look for such aberrations. Fifty-seven patients of benign breast disease were included in this study who were symptomatic for at least 6 months prior to presentation. Detailed serum lipid profile work up was performed on day 1, 15 and 25 of menstrual cycle. The patients with symptoms of maximal severity (or limited to) during leuteal phase of menstrual cycle were included in group I (n = 32). Those who had mastalgia, but did not have above mentioned cyclical variation, were included in group II (n = 25). Since noncyclical mastalgia is a group of heterogeneous disorders of varied etiology, the patients in group II were treated as controls. At day 25, there was an elevation in mean values of HDL-C (P = 0.03) and HDL-C/LDL-C ratio (P = 0.01), and reduction in TC/HDL-C ratio (P < 0.03), in group I. This has not been the case with group II patients. When the patients of mastalgia were treated with low fat dietary regimen, there was a significant difference in the responses of these two groups (P value < 0.0001). Based on the results of lipid profile study and dietary intervention, we conclude that cyclical mastalgia is an entity which is distinctly different from noncyclical mastalgia and needs a different therapeutic approach. Our data, both investigative and therapeutic, suggests that cyclical mastalgia may be a result of cyclical aberrations in lipid metabolism, and the physiological treatment in the form of an appropriate dietary regimen holds a considerable promise.
Intracellular accumulation, subcellular distribution and efflux of tilmicosin in swine phagocytes (1998)

Tilmicosin is a semi-synthetic macrolide antibiotic, currently approved for veterinary use in cattle and swine respiratory disease. As the concentrations of tilmicosin are generally low in swine lung tissue, the interaction of tilmicosin with three types of swine phagocytes (monocyte-macrophages, alveolar macrophages, and neutrophils) was evaluated to provide an understanding of clinical efficacy. After incubation with radiolabelled tilmicosin, uptake was determined and expressed as the ratio of the intracellular (Ci) to the extracellular (Ce) drug concentration (Ci/Ce). Tilmicosin was avidly accumulated by the swine phagocytes (Ci/Ce 48-69 at 4 h incubation) with 51 to 85% localized in the lysosomes. Uptake was dependent on cell viability, temperature and pH, but was not influenced by the metabolic inhibitors, sodium cyanide or potassium fluoride. However, lipopolysaccharide (LPS) exposure increased tilmicosin uptake by the swine phagocytes. In neutrophils, upon removal of extracellular tilmicosin, 60% of the intracellular tilmicosin was effluxed within the first 30 min, but after 4 h of incubation in drug-free medium, 25% remained cell-associated. In contrast, after 4 h of incubation in drug-free medium, 60% and 45% of tilmicosin remained cell-associated, within alveolar macrophages and monocyte-derived macrophages, respectively. Tilmicosin uptake was observed to increase lysosomal enzyme (acid phosphatase, lysozyme and beta-glucuronidase) production. Finally, neutrophils were shown to transport and efflux bioactive tilmicosin in a test system measuring both neutrophil chemotaxis under agarose and a bioassay measuring inhibition of bacterial growth in the presence of antibiotic in agar. These in vitro interactions of tilmicosin with swine phagocytes suggest an integral role in effecting clinical efficacy.
Imaging mass spectrometry (2007)

Imaging mass spectrometry combines the chemical specificity and parallel detection of mass spectrometry with microscopic imaging capabilities. The ability to simultaneously obtain images from all analytes detected, from atomic to macromolecular ions, allows the analyst to probe the chemical organization of a sample and to correlate this with physical features. The sensitivity of the ionization step, sample preparation, the spatial resolution, and the speed of the technique are all important parameters that affect the type of information obtained. Recently, significant progress has been made in each of these steps for both secondary ion mass spectrometry (SIMS) and matrix-assisted laser desorption/ionization (MALDI) imaging of biological samples. Examples demonstrating localization of proteins in tumors, a reduction of lamellar phospholipids in the region binding two single celled organisms, and sub-cellular distributions of several biomolecules have all contributed to an increasing upsurge in interest in imaging mass spectrometry. Here we review many of the instrumental developments and methodological approaches responsible for this increased interest, compare and contrast the information provided by SIMS and MALDI imaging, and discuss future possibilities.