gebhart/patrepeval huggingface dataset:
Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration (2003)

The present study examined the extent and distribution of lymphocyte infiltration in demyelinated lesions in the cerebral cortex of multiple sclerosis (MS) patients. Tissue sections from the brain of 10 MS patients and five patients without neurological disease were double labeled for myelin basic protein and the lymphocyte markers CD3, CD4, CD8, CD45RO, and CD20. The highest density of CD3-positive T cells was found in MS white matter lesions (40.4/10 high power fields (hpf)). Fewer T cells were detected in cortical lesions that extended through both white and gray matter (12.1/10 hpf; P < 0.001). The lowest number of T cells was detected in intracortical demyelinated lesions (1.1/10 hpf). This was equal to the lymphocyte density in nondemyelinated cerebral cortex within the same tissue block (1.1/10 hpf) or cerebral cortex in control brains (1.8/10 hpf). A similar distribution was found using the CD4, CD8, and CD45RO markers. CD20-positive B cells were scarce in all specimens examined. These data indicate that areas of intracortical demyelination in chronic MS are not associated with an increased number of lymphocytes, or an altered distribution of lymphocyte subsets, when compared with control areas in MS and control patients. This finding indicates that the extent of lymphocyte infiltration in MS lesions is dependent on lesion location.
Complementation of a fibre mutant adenovirus by packaging cell lines stably expressing the adenovirus type 5 fibre protein. (1998)

Adenovirus-based gene therapy vectors now in use cannot be targeted to specific cell types in vivo and are immunogenic, properties which limit their clinical utility. Improved vectors lacking the genes for viral structural proteins may overcome these limitations. We have developed cell lines which stably express the adenovirus type 5 (Ad5) fibre protein in its native trimeric form. These cells can complement an Ad5 mutant with a defect in the fibre gene, and are capable of incorporating the Ad5 fibre into particles of a different Ad serotype. As the fibre protein is responsible for the initial binding of virus to cells, packaging cell lines expressing different or modified fibre proteins will be useful in studying the mechanism by which adenovirus infects different cell types.
Structure of the gene for human coagulation factor V (1992)

Activated factor V (Va) serves as an essential protein cofactor for the conversion of prothrombin to thrombin by factor Xa. Analysis of the factor V cDNA indicates that the protein contains several types of internal repeats with the following domain structure: A1-A2-B-A3-C1-C2. In this report we describe the isolation and characterization of genomic DNA coding for human factor V. The factor V gene contains 25 exons which range in size from 72 to 2820 bp. The structure of the gene for factor V is similar to the previously characterized gene for factor VIII. Based on the aligned amino acid sequences of the two proteins, 21 of the 24 intron-exon boundaries in the factor V gene occur at the same location as in the factor VIII gene. In both genes, the junctions of the A1-A2 and A2-A3 domains are each encoded by a single exon. In contrast, the boundaries between domains A3-C1 and C1-C2 occur at intron-exon boundaries, which is consistent with evolution through domain duplication and exon shuffling. The connecting region or B domain of factor V is encoded by a single large exon of 2820 bp. The corresponding exon of the factor VIII gene contains 3106 bp. The 5' and 3' ends of both of these exons encode sequences homologous to the carboxyl-terminal end of domain A2 and the amino-terminal end of domain A3 in ceruloplasmin. There is otherwise no homology between the B domain exons.(ABSTRACT TRUNCATED AT 250 WORDS)
FTO Genotype Is Associated With Exercise Training–induced Changes in Body Composition (2009)

The fat mass (FM) and obesity-associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known whether regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test whether the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO single-nucleotide polymorphism (SNP) rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (P = 0.004) but not in women (P = 0.331; gene-by-sex interaction P = 0.0053). The FTO genotype was associated with body fat responses to regular exercise (P < 0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C allele showed three times greater FM and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity.
Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide (2011)

Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.
Molecular biology of the natriuretic peptides and their receptors. (1992)

After the description in the past 5 years of BNP and CNP, interest in the natriuretic peptide family has dramatically increased. Molecular characterization of the receptors for this hormone family has identified a heterogeneity in the receptor subtypes not previously alluded to by pharmacological or biochemical studies. Much has been published on the physiology of ANP, but the major roles for BNP and CNP remain to be elucidated. Some experiments indicate that ANP and BNP may act synergistically, especially during cardiac stress; however, the high level of structural diversity of BNP among species and the ability of porcine BNP, but not human BNP, to activate human NPR-B suggest that an as yet unidentified receptor may exist that specifically recognizes BNP. Localization studies have implied that CNP is the most prominent neuropeptide in the natriuretic peptide family, and the restriction of its receptor, NPR-B, to the nervous system suggests that CNP and NPR-B may act in the brain to coordinate the central aspects of body fluid homeostasis. Of the three known NPRs, two, NPR-A and NPR-B, are capable of synthesizing their own second messenger, cGMP. The domain within these receptors that has high homology to protein kinases has been demonstrated to be essential for regulating this activity. No kinase activity has been measured in these proteins, but it is possible that this region is important for ATP regulation of guanylyl cyclase activity. This possibility raises interesting parallels with receptor-mediated cAMP signaling within cells. Seven transmembrane receptors, once activated by ligand, associate with G proteins to affect the activity of adenylyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
ChemInform Abstract: The Baeyer‐Villiger Oxidation of Ketones and Aldehydes (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
<title>Digital Radiography: An Overview</title> (1981)

A new class of diagnostic imaging systems, loosely termed Digital Radiography, has emerged during the past year from the laboratory into the forefront of radiological practice. These systems have in common the acquisition of a two dimensional projection image in digital format but include a variety of detectors, techniques and applications. Digital radiography apparatus are conveniently divided into point scanned, line scanned and area systems. Each system is briefly described and its performance capabilities are reviewed. Digital video radiography is given added emphasis due to its rapid development for intravenous angiography. The key requirements and present limitations of major components of the video system are noted. Gross specifications of the next generation of computers for digital radiography are postulated.
Mimicking the Wettability of the Rose Petal using Self-assembly of Waterborne Polymer Particles (2013)

In this work, we present a novel platform to synthesize polymeric “raspberry” particles and explore their use to fabricate surfaces with low wettability and high water adhesion, resembling the properties of naturally occurring surfaces such as the rose petal. The raspberry particles were obtained by layer-by-layer self-assembly of 850 nm core polystyrene particles bearing surface carboxylate groups and corona nanoparticles of different sizes and polymers (polystyrene, poly(para-fluorostyrene) or poly(2,3,4,5,6-penta-fluorostyrene), also bearing surface carboxylates), interleaved with positively charged poly(ally amine) hydrochloride. The raspberry particles were then bound together by covalent coupling of the carboxylate groups with the amine groups of the polymeric interlayer. The films produced by drop-casting the raspberry particles exhibited static water contact angles between ∼135° and ∼146°, depending on the nature of the corona, hysteresis of ∼135° and high adhesion of water droplets. Since all particles were synthesized from scratch by surfactant free emulsion polymerization in air and every step of the protocol was performed in water, this platform is up-scalable and environmentally friendly.
Electrophiles in Foods: The Current Status of Isothiocyanates and Their Chemical Biology (2010)

Unlike many classical signals and hormones, exposure of the cells to electrophilic molecules potentially induces a series of characteristic and wide-ranging biological responses by covalently attaching with macromolecules such as proteins as well as small cellular reductants. In addition to chemicals originated from xenobiotics or lipid peroxidation, electrophiles in foods have recently attracted much attention. These compounds have recently been found to induce expression of cytoprotective proteins that are involved in the elimination or inactivation of oxidative stress and carcinogenic electrophiles implicated in several pathogeneses. The redox-sensitive regulating systems such as Keap1/Nrf2/ARE play a key role in this induction and thus are considered to be the most important target of electrophiles in foods. This review highlights the food-derived electrophiles as promising protectors against various diseases, with an emphasis on possible molecular mechanisms. Current knowledge of isothiocyanates (ITCs), representative electrophile compounds from cruciferous vegetables, is discussed also, with consideration of the chemistry, metabolism, absorption, and factors influencing the biological activities of ITCs. In addition, this review attempts to provide a balanced perspective on the relative beneficial and harmful effects of the food electrophiles.
Activators of coagulation in cultured human lung‐tumor cells (1993)

Tumor matrix generation and tumor cell growth are supported by coagulation processes within the tumor tissue. Activators of coagulation were searched for in suspensions of 9 permanent human squamous-cell lung-cancer (EPLC 32MI, U1752), large-cell lung-cancer (LCLC 97TMI, LCLC 103H, U1810), and small-cell lung-cancer (N-592, H-526, DMS79, 86MI) cell lines. Incubation with these cells shortened the recalcification time in normal plasma (also in the presence of antibodies against tissue factor) or coagulation-factor-VII-, VIII-, IX- or X-deficient plasmas. The activators of coagulation in the 2 most active cell lines (U1752 and LCLC 103H) were further characterized in purified systems: the cleavage of chromogenic substrates, and the generation of markers of pro-thrombin activation were assessed. Three activators of coagulation were found in intact or sonicated cell suspensions and culture supernatants: (i) a tissue factor (TF)-like activity; (ii) an activity activating factor X, which in contrast to "cancer pro-coagulant" was not inhibited by iodoacetamide; and (iii) an activity-activating pro-thrombin, which was inhibited by the serine protease inhibitor PMSF and appeared to require plasmatic co-factor(s). The heterogeneous expression of coagulation activators by lung-tumor cell lines might be of significance for tumor biology and response to therapy.
Direct Generation of Induced Pluripotent Stem Cells from Human Nonmobilized Blood (2010)

The use of induced pluripotent stem cells (iPSCs) is an exciting frontier in the study and treatment of human diseases through the generation of specific cell types. Here we show the derivation of iPSCs from human nonmobilized peripheral blood (PB) and bone marrow (BM) mononuclear cells (MNCs) by retroviral transduction of OCT3/4, SOX2, KLF4, and c-MYC. The PB- and BM-derived iPSCs were quite similar to human embryonic stem cells with regard to morphology, expression of surface antigens and pluripotency-associated transcription factors, global gene expression profiles, and differentiation potential in vitro and in vivo. Infected PB and BM MNCs gave rise to iPSCs in the presence of several cytokines, although transduction efficiencies were not high. We found that 5 × 10(5) PB MNCs, which corresponds to less than 1 mL of PB, was enough for the generation of several iPSC colonies. Generation of iPSCs from MNCs of nonmobilized PB, with its relative efficiency and ease of harvesting, could enable the therapeutic use of patient-specific pluripotent stem cells.
Knocking on FXR's Door:The "Hammerhead"-Structure Series of FXRs Agonists - Amphiphilic Isoxazoles with Potent In Vitro and In Vivo Activities (2014)

The Farnesoid X Receptor (FXR) was recently validated in clinical studies using the bile acid analogue Obeticholic Acid (OCA) as an attractive drug target for liver diseases such as Primary Biliary Cirrhosis (PBC) or Non-alcoholic Steatohepatitis (NASH). OCA, however, turned out to induce cholesterol- related side effects upon prolonged treatment and it shows bile acid like pharmacokinetics. The quest for synthetic non-steroidal FXR agonists with general drug likeliness and improved pharmacokinetic and - dynamic properties has started more than a decade ago: The first non-steroidal and selective FXR agonist with decent submicromolar potency, GW4064, was patented in 1998 and published in 2000. Since then, many pharmaceutical companies have taken GW4064 as a structural template for their efforts in identifying novel patentable FXR agonists with the GW-derived trisubstituted isoxazole general structure. However, so far only one compound out of these different series has made it into the early stages of clinical development: The Px-102/Px-104 from Phenex is currently tested in a phase IIa study in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). In this review we try to summarize from the patent and scientific literature the attempts to improve the GW4064 structure into different directions. Furthermore, we suggest directions for further improvements of this special class of synthetic FXR agonists which all display the typical "hammerhead"-conformation in the FXR ligand binding pocket that provides the basis for their impressive in vitro and in vivo potencies.
Deficiency in activation-induced cytidine deaminase promotes systemic autoimmunity inlprmice on a C57BL/6 background (2009)

Activation-induced deaminase (AID) is a prerequisite for immunoglobulin (Ig) class-switch recombination and somatic hypermutation, which is critical for antibody affinity maturation. IgM and IgG autoantibodies are characteristic of the systemic autoimmune disorders such as lupus. However, the relative contributions of hypermutated high-affinity IgG antibodies and germline-encoded IgM antibodies to systemic autoimmunity are not defined fully. The role of AID in autoimmunity is unclear. The current study used AID-deficient mice to investigate the role of AID in the development and pathogenesis of murine lupus. C57BL/6 mice deficient in both Fas and AID were generated. Compared to their AID-competent littermates, AID(-/-) lymphoproliferative (lpr) mice produced significantly elevated levels of IgM autoreactive antibodies with enhanced germinal centre (GC) response, developed more advanced splenomegaly and exhibited more severe glomerulonephritis. Thus, AID may play an important role in the negative regulation of systemic autoimmune manifestations in murine lupus. The results also indicate that hypermutated high-affinity IgG antibodies are not necessary for the development of autoimmune syndrome in lpr mice on a C57BL/6 background.
Involvement of a serine protease in tumour‐necrosis‐factor‐mediated cytotoxicity (1988)

We investigated the effect of various protease inhibitors on the anti-proliferative and cytotoxic action of tumour necrosis factor (TNF) on mouse L929 fibrosarcoma cells. 1. The following serine-type protease inhibitors led to inhibition of TNF action: phenylmethylsulfonyl fluoride, N alpha-p-tosyl-L-lysine chloromethane, N alpha-p-tosyl-L-phenylalanyl chloromethane, N alpha-p-tosyl-L-arginine methyl ester, L-leucine methyl ester, DL-phenylalanine methyl ester, N-acetyl-DL-phenylalanine-beta-naphthyl ester, p-nitrophenyl p'-guanidino-benzoate and antipain. We could not detect an effect of inhibitors specific for thiol protease on TNF. 2. Inhibition of TNF-mediated cytotoxicity was evident in both the presence and absence of actinomycin D or cycloheximide. 3. TNF itself was not found to be a protease, as it had no proteolytic activity in a sensitive colorimetric assay. [1,3-3H]Diisopropyl fluorophosphate, an effective irreversible inhibitor of serine proteases, did not bind to TNF. Pretreatment of TNF with N alpha-p-tosyl-L-lysine chloromethane did not influence its biological activity. 4. The addition of protease inhibitor to the cells at various times after TNF administration led to a gradual loss of protection, suggesting that the protease acts at a rather late stage. 5. Protease inhibitors did not influence TNF binding, internalization or metabolization. 6. No increase in supernatant protease activity or in cell-associated protease activity could be detected after treatment of L929 cells with TNF. Our results document the involvement of protease activity, acting quite late during the cytolytic and growth inhibiting processes induced by TNF.
A Molecular Shift Register Based on Electron Transfer (1988)

An electronic shift-register memory at the molecular level is described. The memory elements are based on a chain of electron-transfer molecules and the information is shifted by photoinduced electron-transfer reactions. This device integrates designed electronic molecules onto a very large scale integrated (silicon microelectronic) substrate, providing an example of a "molecular electronic device" that could actually be made. The design requirements for such a device and possible synthetic strategies are discussed. Devices along these lines should have lower energy usage and enhanced storage density.
Comparison of the Effects of Mechanical Stimulation on Venous and Arterial Smooth Muscle Cells in vitro (1996)

The proliferation of intimal smooth muscle cells (SMCs) in large muscular arteries and veins often occurs after surgical interventions such as angioplasty and bypass grafting, and may lead to restenosis and graft failure. Clinical observations suggest that increased pulsatile deformation of veins grated into an arterial position may play a role in intimal hyperplasia. Since intimal hyperplasia occurs at the vein/arterial interface of the graft, SMC hyperplasia could be due to the proliferation of either aortic or venous SMCs. Therefore, we compared the effects of in vitro mechanical deformation on the proliferation of aortic SMCs with venous SMCs. Using the Flexercell apparatus (Flexercell Corp., McKeesport, Pa., USA), aortic SMCs, stretched at 3 and 60 cpm did not lead to a significant increase in growth as compared to the nonstretched controls. In contrast, stretch of venous SMCs at 3 and 60 cpm led to a significant increase in growth as compared to the nonstretched controls. These results suggest that the SMC proliferation, as occurs in vein interposition grafts in vivo, may be partially due to a stimulatory response by venous SMCs to increased mechanical stimulation.
Ribonucleotide Reductase Induced by Herpes Simplex Virus has a Virus-specified Constituent (1983)

Ribonucleotide reductase, an enzyme found in all prokaryotic and eukaryotic cells that synthesize DNA, is induced by herpes simplex virus (HSV). In this study the effect of anti-HSV antiserum on the induced ribonucleotide reductase has been examined and the ability of different temperature-sensitive (ts) mutants of HSV-1 to induce the enzyme has been investigated. The HSV-1-induced ribonucleotide reductase was inhibited by antiserum raised against infected cell lysates but not by preimmune serum. The wild-type (ts+) virus induced similar levels of ribonucleotide reductase at 31 degrees C and 38.5 degrees C (the permissive and non-permissive temperatures respectively for the ts mutants). All ts mutants induced approximately wild-type levels of the enzyme at 31 degrees C. At 38.5 degrees C, two of the four ts mutants studied also induced wild-type levels of enzyme but ts G failed to induce any activity while ts K induced variable but low levels. The enzyme activity induced by ts G at 31 degrees C was thermolabile both in vivo and in vitro. These results provide the first strong evidence that the induced ribonucleotide reductase activity is at least partially virus-coded.