gebhart/patrepeval huggingface dataset:
Metoclopramide: a novel adjunct for improving cardiac and hepatocellular functions after trauma-hemorrhage (2000)

Although metoclopramide (MCP) administration after trauma-hemorrhage restores the depressed immune functions, it remains unknown whether this agent has any salutary effects on the depressed cardiovascular and hepatocellular functions under those conditions. Adult male Sprague-Dawley rats underwent a midline laparotomy (i.e., induction of soft-tissue trauma) and were then bled to and maintained at a mean arterial pressure (MAP) of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate (RL). The rats were then resuscitated with four times the shed blood volume in the form of RL over 60 min. MCP (2 mg/kg body wt) or vehicle was administered subcutaneously at the end of resuscitation. At 24 h after resuscitation, cardiac index and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined. Plasma levels of interleukin (IL)-6 and prolactin were also assayed. The results indicate that treatment with MCP after trauma-hemorrhage and resuscitation significantly improved the depressed cardiac output and hepatocellular function. Furthermore, MCP administration significantly increased circulating levels of prolactin and decreased the plasma levels of the proinflammatory cytokine IL-6. Thus, administration of MCP, which increased prolactin secretion, appears to be a useful adjunct for restoring the depressed cardiac and hepatocellular functions and downregulating inflammatory cytokine release after trauma and hemorrhagic shock.
VX-950, a Novel Hepatitis C Virus (HCV) NS3-4A Protease Inhibitor, Exhibits Potent Antiviral Activities in HCV Replicon Cells (2006)

The NS3-4A serine protease of hepatitis C virus (HCV) is essential for viral replication and therefore has been one of the most attractive targets for developing specific antiviral agents against HCV. VX-950, a highly selective, reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, is currently in clinical development for the treatment of hepatitis C. In this report, we describe the in vitro characterization of anti-HCV activities of VX-950 in subgenomic HCV replicon cells. Incubation with VX-950 resulted in a time- and dose-dependent reduction of HCV RNA and proteins in replicon cells. Moreover, following a 2-week incubation with VX-950, a reduction in HCV RNA levels of 4.7 log(10) was observed, and this reduction resulted in elimination of HCV RNA from replicon cells, since there was no rebound in replicon RNA after withdrawal of the inhibitor. The combination of VX-950 and alpha interferon was additive to moderately synergistic in reducing HCV RNA in replicon cells with no significant increase in cytotoxicity. The benefit of the combination was sustained over time: a 4-log(10) reduction in HCV RNA level was achieved following a 9-day incubation with VX-950 and alpha interferon at lower concentrations than when either VX-950 or alpha interferon was used alone. The combination of VX-950 and alpha interferon also suppressed the emergence of in vitro resistance mutations against VX-950 in replicon cells.
Introduction to Physical Polymer Science (2005)

Chain Structure and Configuration. Molecular Weights and Sizes. Concentrated Solutions and Phase Separation Behavior. The Amorphous State. The Crystalline State. Polymers in the Liquid Crystalline State. Glass-Rubber Transition Behavior. Cross-Linked Polymers and Rubber Elasticity. Polymer Viscoelasticity and Rheology. Mechanical Behavior of Polymers. Modern Topics. Index.
Failure of Dual Antimicrobial Therapy in Treatment of Gonorrhea (2016)

Increasing antibacterial resistance in Neisseria gonorrhoeae is threatening the success of routine treatment. This letter describes the clinical failure of ceftriaxone and azithromycin in a patient with gonorrhea.
Anti‐biofilm efficacy of a lactoferrin/xylitol wound hydrogel used in combination with silver wound dressings (2011)

With an epidemic increase in obesity combined with an ageing population, chronic wounds such as diabetic foot ulcers, pressure ulcers and venous leg ulcers are an increasing clinical concern. Recent studies have shown that bacterial biofilms are a major contributor to wound bioburden and interfere with the normal wound healing process; therefore, rational design of wound therapies should include analysis of anti-biofilm characteristics. Studies using the combined treatment of bacterial biofilms with the innate immune molecule lactoferrin and the rare sugar-alcohol xylitol have demonstrated an antimicrobial capacity against a clinical wound isolate. Studies presented here used a colony-drip-flow reactor biofilm model to assess the anti-biofilm efficacy of a lactoferrin/xylitol hydrogel used in combination with commercially available silver-based wound dressings. Log reductions in biofilm viability are compared with a commercially available wound hydrogel used in combination with the silver-based wound dressings. For both a single species biofilm and a dual species biofilm, the lactoferrin/xylitol hydrogel in combination with the silver wound dressing Acticoat™ had a statistically significant reduction in biofilm viability relative to the commercially available wound hydrogel. This study also demonstrated a statistical interaction between the lactoferrin/xylitol hydrogel and the silver wound dressing.
A novel light‐ and heat‐responsive regulation of the groE transcription in the absence of HrcA or CIRCE in cyanobacteria (2007)

The inactivation of the hrcA gene resulted in de-repression of the two CIRCE-containing groE genes in a cyanobacterium Synechocystis sp. strain PCC6803, indicating that the CIRCE operator/HrcA repressor system operates in the cyanobacterium. We found that the groE expression in the hrcA mutant is greatly induced by heat and/or light. Removal of a K-box containing and an N-box containing region upstream of the groESL1 promoter abolished light-induced transcription of a luxAB reporter gene fused with the groESL1 promoter. Similar sequences to the K-box, GTTCGG-NNAN-CCNNAC, were also found upstream of the dnaK2 genes. A specific binding of a protein(s) to the N-box, GATCTA, was detected by a gel mobility shift assay with using cell extracts. We propose that the cyanobacterial groEL expression is regulated by a putative positive mechanism mediated by these novel elements in addition to the HrcA/CIRCE system. The groEL2 genes from Synechococcus sp. strain PCC 7942 and Thermosynechococcus elongatus, which lack CIRCE, K-box, and N-box naturally, were also induced by heat and/or light, indicating that the control mechanism of the unique light-responsive groE expression is highly diversified in cyanobacteria.
Polyglycolic Acid-Induced Inflammation: Role of Hydrolysis and Resulting Complement Activation (2006)

Tissue and organ replacement have quickly outpaced available supply. Tissue bioengineering holds the promise for additional tissue availability. Various scaffolds are currently used, whereas polyglycolic acid (PGA), which is currently used in absorbable sutures and orthopedic pins, provides an excellent support for tissue development. Unfortunately, PGA can induce a local inflammatory response following implantation. Therefore, we investigated the molecular mechanism of inflammation in vitro and in vivo. Degraded PGA induced an acute peritonitis, characterized by neutrophil (PMN) infiltration following intraperitoneal injection in mice. Similar observations were observed using the metabolite of PGA, glycolide. Dissolved PGA or glycolide, but not native PGA, activated the classical complement pathway in human sera, as determined by classical complement pathway hemolytic assays, C3a and C5a production, and C3 and immunoglobulin deposition. To investigate whether these in vitro observations translated to in vivo findings, we used genetically engineered mice. Intraperitoneal administration of glycolide or dissolved PGA in mice deficient in C1q, factor D, C1q and factor D, or C2 and factor B demonstrated significantly reduced PMN infiltration compared to congenic controls (WT). Mice deficient in C6 also demonstrated acute peritonitis. However, treatment of WT or C6 deficient mice with a monoclonal antibody against C5 prevented the inflammatory response. These data suggest that the hydrolysis of PGA to glycolide activates the classical complement pathway. Furthermore, complement is amplified via the alternative pathway and inflammation is induced by C5a generation. Inhibition of C5a may provide a potential therapeutic approach to limit the inflammation associated with PGA-derived materials following implantation.
Microcirculatory Changes in Term Newborns with Suspected Infection: An Observational Prospective Study (2013)

Background. In adults severely disturbed microcirculatory flow can be observed by Orthogonal Polarized Spectral (OPS) imaging techniques during sepsis. Therefore we set out to assess for microcirculatory changes in term newborns with suspected early onset infection using OPS. Methods. OPS images were obtained prospectively from the vascular bed of the ear conch and upper arm of 47 newborns on their 1st, 2nd, and 3rd day of life. OPS sequences were analyzed semiquantitatively offline and blinded to clinical status of the infant. Flow in vessels was classified as continuous or noncontinuous flow and given as proportion of total vessels per image as in the studies in adults. Results. The proportion of vessels with continuous flow was significantly lower in the infants with infection (69% [56-81] versus 90% [87-94] (P = 0.0003)). None of the infants with infection was in shock or severely septic. Conclusion. In term neonates the microcirculatory flow is impaired in a large proportion of vessels even in mild to moderate infection. These changes can be observed at the onset of disease at the external ear, an optimal site for microcirculatory measurements in term infants.
Glial expression of estrogen and androgen receptors after rat brain injury (2002)

Estrogens and androgens can protect neurons from death caused by injury to the central nervous system. Astrocytes and microglia are major players in events triggered by neural lesions. To determine whether glia are direct targets of estrogens or androgens after neural insults, steroid receptor expression in glial cells was assessed in two different lesion models. An excitotoxic injury to the hippocampus or a stab wound to the parietal cortex and hippocampus was performed in male rats, and the resultant expression of steroid receptors in glial cells was assessed using double-label immunohistochemistry. Both lesions induced the expression of estrogen receptors (ERs) and androgen receptors (ARs) in glial cells. ERalpha was expressed in astrocytes immunoreactive (ERalpha-ir) for glial fibrillary acidic protein or vimentin. AR immunoreactivity colocalized with microglial markers, such as Griffonia simplicifolia lectin-1 or OX-6. The time course of ER and AR expression in glia was studied in the stab wound model. ERalpha-ir astrocytes and AR-ir microglia were observed 3 days after lesion. The number of ERalpha-ir and AR-ir glial cells reached a maximum 7 days after lesion and returned to low levels by 28 days postinjury. The studies of ERbeta expression in glia were inconclusive; different results were obtained with different antibodies. In sum, these results suggest that reactive astrocytes and reactive microglia are a direct target for estrogens and androgens, respectively.
Identification of betacellulin as a major peptide growth factor in milk: purification, characterization and molecular cloning of bovine betacellulin (1999)

Betacellulin (BTC), a member of the epidermal growth factor (EGF) family of peptide growth factors, was purified from a growth-factor-enriched whey fraction of bovine milk by a combination of ion-exchange chromatography, gel-filtration chromatography, affinity chromatography and reverse-phase HPLC. Bovine BTC (bBTC) had an apparent molecular mass of 21-22 kDa on SDS/PAGE and exists in a glycosylated form. The cDNA encoding bBTC was obtained by a combination of 5ʹ and 3ʹ rapid amplification of cDNA ends (‘RACE’). The primary translation product consists of 178 amino acid residues containing a putative signal sequence, a transmembrane domain, the mature BTC domain and a cytoplasmic domain containing a highly hydrophilic Arg-Lys-rich region similar to that of mouse BTC and human BTC. The amino acid sequence of the bBTC precursor was 88% identical with human BTC and 79% identical with mouse BTC. The bBTC gene was found to be expressed in a wide range of tissues, including the mammary gland. The identification of BTC in milk raises the possibility that it has a major role in the growth and development of the neonatal gastrointestinal tract.
Inhibitory Tyrosine Protein Kinase p50 Is Associated with Protein-tyrosine Phosphatase PTP-PEST in Hemopoietic and Non-hemopoietic Cells (1997)

p50(csk) is a cytosolic tyrosine protein kinase expressed in all cell types. Accumulating data show that it inhibits multiple cellular processes, as a consequence of its ability to repress the enzymatic activity of Src family tyrosine protein kinases. We previously demonstrated that, via its Src homology 3 (SH3) domain, Csk is tightly bound to PEP, a protein-tyrosine phosphatase (PTP) exclusively expressed in hemopoietic cells. In this report, we have tested the possibility that Csk also interacts with PTP-PEST, a ubiquitous PTP sharing structural homology with PEP. Our studies revealed that Csk was associated with PTP-PEST in a variety of cell types, including non-hemopoietic cells. This interaction involved the SH3 region of p50(csk) and a proline-rich region (PPPLPERTPESFVLADM) outside the catalytic region of PTP-PEST. Even though both PTP-PEST and PEP were associated with Csk, significant differences were noted between these two PTPs. PTP-PEST, but not PEP, was also complexed with Shc, an adaptor molecule implicated in the Ras pathway. Moreover, PTP-PEST and PEP were found to accumulate primarily in distinct intracellular compartments in cell fractionation studies. In combination, these findings indicated that, like PEP, PTP-PEST is probably involved in Csk-mediated functions in mammalian cells. Moreover, they suggested that the roles of Csk-PTP-PEST and Csk-PEP are likely to be different.
Learning Invariance from Transformation Sequences (1991)

The visual system can reliably identify objects even when the retinal image is transformed considerably by commonly occurring changes in the environment. A local learning rule is proposed, which allows a network to learn to generalize across such transformations. During the learning phase, the network is exposed to temporal sequences of patterns undergoing the transformation. An application of the algorithm is presented in which the network learns invariance to shift in retinal position. Such a principle may be involved in the development of the characteristic shift invariance property of complex cells in the primary visual cortex, and also in the development of more complicated invariance properties of neurons in higher visual areas.
Synthesis of a Protein‐Reactive ATP Analog and Its Application for the Affinity Labeling of Rabbit‐Muscle Actin (1974)

The synthesis of a protein‐reactive ATP analog, S ‐dinitrophenyl‐6‐mercaptopurine riboside 5′‐triphosphate, started from isopropylidated 6‐mercaptopurine. After dinitrophenylation, the thioester riboside was phosphorylated with POCI 3 and the monophosphate was converted to the triphosphate by activation with the aid of phosphoric acid diphenylester chloride, and reaction with inorganic pyrophosphate. The analog, labelled with 32 P in the β and γ‐positions, was used for covalent binding of the nucleotide to rabbit muscle actin. In preparation for this affinity labelling, the one superficial—SH group of the protein had been alkylated with N ‐ethylmaleimide. The nucleotide was able to depolymerize N ‐ethylmaleimide‐F‐actin, and became attached to the G‐form at a ratio of 0.8 molecules per actin monomer. The product could be repolymerized to the F‐form with liberation of inorganic phosphate. The product could not be depolymerized after that by ATP solutions at low ionic strength. A single radioactively labelled peptide was discerned in fingerprints of a tryptic digest.
Pulmonary deposition and clearance of aerosolized interferon (1984)

Small particle aerosols of a hybrid DNA recombinant human alpha interferon, A/D bgl, and a related DNA recombinant leukocyte interferon, A, were generated and delivered to mice for 23.5 h a day for 4 consecutive days. The antiviral activity of these interferons in delivery reservoirs, in the aerosols generated, and in the lungs of test mice was monitored during and after aerosol administration in cytopathic effect inhibition assays, using vesicular stomatitis virus as the indicator virus. In addition, the activity of these interferons in primary mouse embryo cells against influenza A/HK/68 (H3N2) virus was determined. The results obtained indicated that the interferon particles generated in the continuous aerosol therapy system used in these studies remained biologically active and could be readily detected in both aerosol mists and lungs of test mice; levels of exogenous interferon in the lungs equalled or exceeded levels of interferons produced endogenously during experimentally induced influenza virus infection. Titers of the exogenously administered interferons decreased gradually and disappeared from the lungs between 24 and 48 h after cessation of aerosolization. Recombinant human alpha interferon A/D, but not recombinant leukocyte alpha interferon A, significantly inhibited replication of A/HK/68 virus in primary mouse embryo cells in the in vitro studies.
In vivopriming of T cells against cryptic determinants by dendritic cells exposed to interleukin 6 and native antigen (1998)

T cells recognizing poorly displayed self determinants escape tolerance mechanisms and persist in the adult repertoire. The process by which these T cells are primed is not clear, but once activated, they can cause autoimmunity. Here, we show that dendritic cells treated with interleukin 6 (IL-6) process and present determinants from a model native antigen in a qualitatively altered hierarchy, activating T cells in vitro and in vivo against determinants that were previously cryptic because of poor display. IL-6 does not induce conventional maturation of dendritic cells but alters the pH of peripheral, early endosomal compartments and renders the cells more susceptible to killing by chloroquine. Acidification of endosomes by ouabain mimics the effect of IL-6 and allows processing of the same cryptic determinant. These results suggest that cytokines such as IL-6 could initiate and help to propagate an autoimmune disease process by differentiating dendritic cells into a state distinct from that induced by normal maturation.
IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells (2006)

Constitutive expression of IL9 in the lungs of transgenic (Tg) mice resulted in an asthma-like phenotype consisting of lymphocytic and eosinophilic lung inflammation, mucus hypersecretion and mast cell hyperplasia. Several T(h)2 cytokines including IL4, IL5 and IL13 were expressed in the lung in response to Tg IL9. IL13 was absolutely necessary for the development of lung pathology. To understand how IL9 induces IL13-dependent lung inflammation and mucus production, we sought the IL13-producing cells. Surprisingly, we found that the absence of T cells and B cells in recombinase-activating gene 1 (RAG1)-deficient IL9 Tg mice enhanced lung inflammation and dramatically enhanced IL13 production. In addition, the lack of mast cells or eosinophils in IL9 Tg mice did not affect IL13 levels in the lung. In situ hybridization for IL13 on lung sections from RAG1-/- IL9 Tg mice revealed that airway epithelial cells were the major IL13-producing cell type. Our results implicate the lung epithelium as a potentially important source of inflammatory cytokines in asthma.
Mapping of a gene coding for a major late structural polypeptide on the vaccinia virus genome (1984)

Cell-free translation of total RNA isolated from vaccinia virus-infected cells late in infection results in a complex mixture of polypeptides. A monospecific antibody directed against one of the major structural proteins of the virus particle immunoprecipitated a single polypeptide with a molecular weight of 11,000 (11K) from this mixture. Immunoprecipitation was therefore used to identify the structural polypeptide among the in vitro translation products of RNA purified by hybridization selection to restriction fragments of the vaccinia virus genome. This allowed us to map the mRNA coding for the 11K polypeptide to the extreme left-hand end of the HindIII E fragment. Detailed transcriptional mapping of this region of the genome by nuclease S1 analysis revealed the presence of a late RNA transcribed from the rightward-reading strand. Its 5' end mapped at ca. 130 base pairs to the left of the HindIII site at the junction between the HindIII F and E fragments. The map position of this RNA coincided precisely with the map position of the late message coding for the 11K polypeptide.
Collagen; ultrastructure and its relation to mechanical properties as a function of ageing (1972)

Abstract Tail tendons from Fischer and Sprague-Dawly albino rats of ages from 2 weeks to 3 years were investigated under the polarizing microscope as regards structure and deformation behaviour. Periodically extinguishing bands were observed along the otherwise featureless tendons. By analysing the behaviour of this extinction pattern under appropriate rotations of the tendon, it could be deduced that the orientation of the basic birefringent units varies periodically along the tendon and that this periodic pattern corresponds to a planar arrangement of the anisotropic entities. All the relevant parameters of this periodic structure could be determined in a representative manner from polarizing optics alone. Subdivision of the tendons revealed regularly undulating or rather crimped subunits in good correspondence to what has been deduced from the extinction bands in the intact tendons. The crimp angle was found to decrease while the periodicity increased - in approximate proportion to the length of the tail - with the age of the rat implying constancy of crimp number during the life time of the animal. On elongation the periodicity was gradually removed. The calculated fibre elongation necessary to eliminate the crimp was in good agreement with observation for mature rats but was larger for young rats implying the simultaneous stretching of the fibre itself. Stress-strain properties of tendons were measured and models for crimp straightening were tested. It was found that a model containing inflexible hinges, corresponding to the ‘elastica’ problem in mechanics gave reasonable fit with experiment. Analysis of stress-strain data on this basis leads to a basic load bearing unit, the diameter of which increases from 100 to 500 nm with the age of the animal. Implications of these findings for the structure and properties of the tendons, also in relation to ageing are pointed out.
Wide‐field optically sectioning fluorescence microscopy with laser illumination (2000)

We describe an extremely simple method by which optically sectioned fluorescence images may be obtained with conventional microscopes using laser illumination. A one-dimensional grid pattern is introduced into the illumination system, together with a rotating ground glass diffuser. This causes an image of the grid pattern to be projected into the specimen. Images taken at three spatial positions of the grid are processed in a simple manner to provide optically sectioned images of fluorescent specimens.