gebhart/patrepeval huggingface dataset:
Virucidal Treatment of Blood Protein Products with UVC Radiation (1997)

The virus safety of blood derivatives continues to be of concern, especially with respect to nonenveloped and/or heat-stable viruses. Previously, we demonstrated that treatment of whole plasma, AHF concentrate or fibrinogen with short wavelength ultraviolet light (UVC) results in the inactivation of > or = 10(6) infectious doses (ID) of encephalomyocarditis virus (EMCV), hepatitis A virus (HAV) and porcine parvovirus (PPV), each of which is nonenveloped. Protein recovery was enhanced greatly by inclusion of the flavonoid, rutin, added prior to UVC exposure to quench reactive oxygen species. We now report on the treatment of albumin and intravenous immune globulin (IVIG) isolated by a previously described, integrated chromatographic method. Albumin was treated with either 0.1 or 0.2 J/cm2 UVC in the presence of 0.8 or 1.6 mM rutin; IVIG was treated with either 0.05 or 0.1 J/cm2 UVC in the presence of 0.5 or 1.0 mM rutin. Our results show that > or = 10(6.9) ID of EMCV and PPV were inactivated under each of the conditions studied except the treatment of albumin with 0.1 J/cm2 UVC in the presence of 1.6 mM rutin where 10(4.3) ID of EMCV and > or = 10(6.9) ID of PPV were killed. It appears that the sensitivity of PPV to UVC exceeds that of EMCV and that virus kill with UVC is higher in IVIG than in albumin. In the absence of rutin, UVC increased the extent of aggregation of both albumin and IVIG by two- to three-fold. With rutin present, the increase in albumin aggregation was reduced, and it was virtually eliminated by subsequent processing on Sephacryl S-200, a step in the existing procedure designed to remove aggregates. The increase in aggregation of IVIG appeared to be eliminated on inclusion of either 0.5 mM or 1 mM rutin. We conclude that both albumin and IVIG can be treated with UVC to inactivate > or = 10(6) ID of nonenveloped viruses. The inclusion of rutin during treatment helps protect against protein aggregation.
Differences and similarities between chronic obstructive pulmonary disease and asthma (1999)

Asthma and chronic obstructive pulmonary disease (COPD) are complex conditions with imprecise definitions, which make definitive morphological comparisons difficult. The airways in asthma are occluded by tenacious plugs of exudate and mucus, and there is fragility of airway surface epithelium, thickening of the reticular layer beneath the epithelial basal lamina (the last two not usually features of COPD), and bronchial vessel congestion and oedema. There is an increased inflammatory infiltrate comprising 'activated' lymphocytes and eosinophils with release of granular content in the latter, and enlargement of bronchial smooth muscle, particularly in medium-sized bronchi. CD4+ve lymphocytes predominate over CD8+ve cells and neutrophils are sparse. In contrast, three conditions contribute to COPD. In chronic bronchitis there is cough and mucous hypersecretion with enlargement of tracheobronchial submucosal glands and a disproportionate increase of mucous acini. CD8+ve lymphocytes predominate over CD4+ve cells and there are increased numbers of subepithelial macrophages and intra-epithelial neutrophils. Exacerbations of bronchitis are associated with a tissue eosinophilia, apparent absence of IL-5 protein but gene expression for IL-4 and IL-5 is present. In small or peripheral airways disease, there is inflammation of bronchioli and mucous metaplasia and hyperplasia, with increased intraluminal mucus, increased wall muscle, fibrosis, and airway stenoses (also referred to as chronic obstructive bronchiolitis). Respiratory bronchiolitis involving increased numbers of pigmented macrophages is a critically important early lesion. Increasingly severe peribronchiolitis includes infiltration of T lymphocytes in which the CD8+ subset again predominates. These inflammatory changes may predispose to the development of centrilobular emphysema and reduced FEV1 via the destruction of alveolar attachments. In emphysema there is abnormal, permanent enlargement of airspaces distal to the terminal bronchiolus (i.e. within the acinus) accompanied by destruction of alveolar walls and without obvious fibrosis. The severity of emphysema, rather than type, appears to be the most important determinant of chronic deterioration of airflow, and in this there may be significant loss of elastic recoil and microscopic emphysema prior to the observed macroscopic destruction of the acinus.
Paper or Screen, Mother Tongue or English: Which Is Better? (2002)

The medium (paper vs screen) did not influence the ability of family physicians to retain medical information. They best retained medical information when reading in their mother tongue.
Identification and function of A1 adenosine receptors in normal and cystic fibrosis human airway epithelial cells (1995)

A role for adenosine in the regulation of ion transport in pulmonary epithelial cells has recently been proposed. Although evidence exists documenting the presence and function of adenosine A2 receptors in airway epithelia, the presence of adenosine A1 receptors remains controversial. The present study used reverse transcriptase-polymerase chain reaction (PCR) and whole cell patch-clamp analysis to investigate A1 receptor presence and function in normal and cystic fibrosis (CF) human airway epithelial cells. Oligonucleotide primers complementary to the human brain A1 receptor sequence generated a PCR product of the predicted size (311 bp) in normal tracheal (9HTEo-) and CF submucosal (2CFSMEo-) airway cell lines and in primary cultures of CF nasal polyp epithelial cells. An oligonucleotide probe internal to the PCR primers hybridized with the 311-bp cDNAs by Southern blot analysis. cDNA sequencing demonstrated that the normal and CF airway cell PCR products are 100% identical to the corresponding sequence of the human brain adenosine A1 receptor. Northern blot analysis of 9HTEo-and 2CFSMEo- poly(A)+ RNA revealed the presence of two bands of approximately 3.0 and approximately 5.5 kb corresponding to the A1 receptor. Whole cell patch-clamp analyses demonstrated that 8-cyclopentyl-1,3-dipropylxanthine, a specific A1 receptor antagonist, increases adenosine 3',5'-cyclic monophosphate (cAMP)-activated Cl- conductance in 9HTEo-airway cells and allows cAMP to increase Cl- conductance in 2CFSMEo- CF airway cells and CF nasal polyp epithelial cells in primary culture. These results provide evidence for the presence and function of A1 receptors in normal and CF airway epithelial cells and provide support for a role of adenosine A1 receptors in modulating airway epithelial cell Cl- transport.
The Effects of Perioperatively Administered Colloids and Crystalloids on Primary Platelet-Mediated Hemostasis and Clot Formation (2002)

Our data suggest that during deliberate colloid administration, critically impaired fibrinogen polymerization and reduced fibrinogen concentrations might be reached earlier than expected. Therefore, maintaining fibrinogen concentrations seems essential when continuing blood loss is bridged by colloid infusion until transfusion triggers are reached, especially in patients already exhibiting borderline fibrinogen levels at baseline.
Mutant Epidermal Growth Factor Receptors as Targets for Cancer Therapy (2002)

The epidermal growth factor (EGF) receptor is overexpressed in many cancers, and is under intensive investigation as a target for cancer therapy. Cancer cells have also been shown to express mutated EGF receptors; these are potentially highly specific targets for cancer therapeutics, as they have not been detected in any normal adult tissues. The most common of these mutant EGF receptors, EGFRvIII, is one in which amino acids 6 - 273 of the extracellular domain are deleted. This specific mutation is common in glioblastoma and in several other types of cancer, and has been shown to promote aggressive growth of tumors in vivo. The loss of part of the extracellular domain results in a receptor that has constitutive tyrosine kinase activity. Current evidence suggests that EGFRvIII has altered signalling properties compared to normal EGF receptor. The mutation in EGFRvIII also creates a new, cancer cell-specific epitope. This epitope is extracellular and therefore represents a very promising target for antibody-directed therapeutics. This review covers our current understanding of the properties of EGFRvIII, and recent developments in the characterization and therapeutic application of EGFRvIII-specific antibodies.
Cytotoxic effects of sigma ligands: sigma receptor-mediated alterations in cellular morphology and viability (1995)

The morphological effects of several neuroleptics as well as other novel and prototypic sigma ligands were examined by addition to cultures of C6 glioma cells. Sigma ligands caused loss of processes, assumption of spherical shape, and cessation of cell division. The time course and magnitude of this effect were dependent on the concentration of sigma ligand. Continued exposure to sigma compounds ultimately resulted in cell death. However, the morphological effect was reversible when sigma ligand was removed shortly after rounding. The potency of compounds to produce these effects generally correlated with binding affinity at sigma receptors of C6 glioma cell membranes labeled with [3H](+)-pentazocine. At a concentration of 100 microM, haloperidol, reduced haloperidol, fluphenazine, perphenazine, trifluoperazine, BD737, LR172, BD1008, and SH344 produced significant effects in 3–6 hr of exposure. Other compounds, such as trifluperidol, thioridazine, and (-)-butaclamol, produced significant effects by 24 hr of exposure. Despite the requirement of micromolar concentrations of ligand (some compounds were effective at 30 microM), the effect showed a remarkable specificity for compounds exhibiting sigma receptor binding affinity. Neuroleptics lacking potent sigma affinity [e.g., (-)- sulpiride, (+)-butaclamol, and clozapine] and other compounds that lack significant sigma affinity but that are agonists or antagonists at dopamine, serotonin, adrenergic, glutamate, phencyclidine, GABA, opiate, or muscarinic cholinergic receptors were without effect on cellular morphology at concentrations up to 300 microM over a period of 72 hr. Likewise, blockers and activators of Na+, K+, and Ca2+ channels and a monoamine oxidase inhibitor devoid of sigma affinity were without effect. Interestingly, 1,3-di-o-tolylguanidine (DTG), (+)-3-(3- hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP], (+)-pentazocine, (+)- cyclazocine, and other sigma-active benzomorphans and morphinans appeared inactive in up to 72 hr of culture. However, these compounds interacted synergistically with a subeffective dose of BD737 (30 microM) to produce effects usually in 6 hr or less. Also, the pH of the culture medium had a profound effect on the activity of sigma compounds. Increasing the pH from the normal range of 7.2–7.4 to pH 8.3– 8.5 shifted the dose curves (30, 100, 300 microM) for all sigma compounds to the left. Under these conditions, DTG, (+)-3-PPP, and benzomorphans produced effects in 24 hr or less.(ABSTRACT TRUNCATED AT 400 WORDS)
Epidemiology of meningitis and bacteraemia due to Streptococcus pneumoniae in The Netherlands (2000)

In The Netherlands, accurate data on the epidemiology of pneumococcal meningitis are available through a clinical microbiology laboratory-based national surveillance of cerebrospinal fluid isolates. The Netherlands Reference Laboratory for Bacterial Meningitis receives isolates of about 80% of all meningitis cases and about 40% of bacteraemic cases. The incidence of pneumococcal meningitis has increased slowly from 1.0/100000 in 1990 to 1.5/100000 since 1996. The highest age-specific incidence of meningitis was observed in children <5y of age (8.2/100000 in 1999). Of all isolates, 35% were from children <5 y of age. The number of isolates from non-meningitis patients with bacteraemia increased considerably since the early 1990s, especially among the elderly. The highest incidence was found in 1996, probably owing to a relatively severe winter. During 1995–1999, pneumococcal meningitis in The Netherlands was caused mainly by serotypes 3, 6B, 7F, 9V, 14, 18C, 19F, and 23F. Of the cases in children <15y, almost half were caused by serotypes 6B, 14, 18C, and 19F. The serotypes present in the 23-valent polysaccharide and 7-valent conjugate vaccines accounted for 87% and 47% of all meningitis cases, respectively. Pneumococcal resistance to penicillin in The Netherlands is still low, at about 1%. Genotypically, resistant strains belong to many clones. Horizontal transfer of capsular genes occurs among these isolates. In The Netherlands, 45% of cases of pneumococcal meningitis have severe predisposing factors. The case-fatality rate was significantly higher among patients with impaired immunity than among those with a break in the integrity of the dura.
Involvement of Interleukin-10 (IL-10) and Viral IL-6 in the Spontaneous Growth of Kaposi’s Sarcoma Herpesvirus-Associated Infected Primary Effusion Lymphoma Cells (1999)

Primary effusion lymphoma (PEL) is a distinct type of lymphoma associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. To determine the factors responsible for the unrestrained proliferation of PEL, we have studied the growth factor requirements of the PEL-derived BCBL-1 and BC-1 cell lines. Both cell lines were found to be autocrine growth factor dependent and to release human interleukin-6 (IL-6), viral IL-6 (vIL-6), and human IL-10 in the culture supernatant. To establish whether these cytokines contribute to autocrine growth, neutralizing antibodies against human IL-6, vIL-6, human IL-10, and soluble IL-10 receptor were used. These experiments showed that human IL-10 and, to a lesser degree, vIL-6 serve as autocrine growth factors for BCBL-1 and BC-1 cells. Thus, human IL-10 and vIL-6 are growth factors released and used by PEL cells for autonomous proliferation and may be critical to the development and progression of PEL.
Immobilization of Cells with Surface-Displayed Chitin-Binding Domain (2006)

To explore chitin-binding domain (ChBD)-based cell immobilization, a tripartite gene fusion consisting of an in-frame fusion of ChBD to lpp and ompA was constructed and expressed in Escherichia coli. ChBD-displayed cells exhibited highly specific and stable binding to chitin within a wide range of pHs (5 to 8) and temperatures (15 to 37 degrees C). These results illustrate the promising use of this approach for engineering applications.
The eIF4G-eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase (1996)

The 2A proteinases (2Apro) of certain picornaviruses induce the cleavage of the eIF4G subunit of the cap-binding protein complex, eIF4F. Several reports have demonstrated that 2Apro of rhinovirus and coxsackievirus B4 cleave eIF4G directly. However, it was suggested that in poliovirus infection, the 2Apro induces the activation of a cellular proteinase which in turn cleaves eIF4G. Furthermore, it is not clear whether eIF4G is cleaved as part of the eIF4F complex or as an individual polypeptide. To address these issues, recombinant eIF4G was purified from Sf9 insect cells and tested for cleavage by purified rhinovirus 2Apro. Here we report that eIF4G alone is a relatively poor substrate for cleavage by the rhinovirus 2Apro. However, an eIF4G-eIF4E complex is cleaved efficiently by the 2Apro, suggesting that eIF4F is a preferred substrate for cleavage by rhinovirus 2Apro. Furthermore, 2Apr drastically reduced the translation of a capped mRNA. An eIF4G-eIF4E complex, but not eIF4G alone, was required to restore translation.
Suprachiasmatic GABAergic Inputs to the Paraventricular Nucleus Control Plasma Glucose Concentrations in the Rat via Sympathetic Innervation of the Liver (2004)

Daily peak plasma glucose concentrations are attained shortly before awakening. Previous experiments indicated an important role for the biological clock, located in the suprachiasmatic nuclei (SCN), in the genesis of this anticipatory rise in plasma glucose concentrations by controlling hepatic glucose production. Here, we show that stimulation of NMDA receptors, or blockade of GABA receptors in the paraventricular nucleus of the hypothalamus (PVN) of conscious rats, caused a pronounced increase in plasma glucose concentrations. The local administration of TTX in brain areas afferent to the PVN revealed that an important part of the inhibitory inputs to the PVN was derived from the SCN. Using a transneuronal viral-tracing technique, we showed that the SCN is connected to the liver via both branches of the autonomic nervous system (ANS). The combination of a blockade of GABA receptors in the PVN with selective removal of either the sympathetic or parasympathetic branch of the hepatic ANS innervation showed that hyperglycemia produced by PVN stimulation was primarily attributable to an activation of the sympathetic input to the liver. We propose that the daily rise in plasma glucose concentrations is caused by an SCN-mediated withdrawal of GABAergic inputs to sympathetic preautonomic neurons in the PVN, resulting in an increased hepatic glucose production. The remarkable resemblance of the presently proposed control mechanism to that described previously for the control of daily melatonin rhythm suggests that the GABAergic control of sympathetic preautonomic neurons in the PVN is an important pathway for the SCN to control peripheral physiology.
The murine IL-13 receptor alpha 2: molecular cloning, characterization, and comparison with murine IL-13 receptor alpha 1. (1998)

Two components of a receptor complex for IL-13, the IL-4R and a low affinity IL-13-binding chain, IL-13R alpha 1, have been cloned in mice and humans. An additional high affinity binding chain for IL-13, IL-13R alpha 2, has been described in humans. We isolated a cDNA from the thymus that encodes the murine orthologue of the human IL-13R alpha 2. The predicted protein sequence of murine IL-13R alpha 2 (mIL-13R alpha 2) has 59% overall identity to human IL-13R alpha 2 and is closely related to the murine low affinity IL-13-binding subunit, IL-13R alpha 1. The genes for both mIL-13-binding chains map to the X chromosome. A specific interaction between mIL-13R alpha 2.Fc protein and IL-13 was demonstrated by surface plasmon resonance using a BIACORE instrument. Ba/F3 cells that were transfected with mIL-13R alpha 2 expressed 5000 molecules per cell and bound IL-13 with a single Kd of 0.5 to 1.2 nM. However, these cells did not proliferate in response to IL-13, and the IL-4 dose response was unaffected by high concentrations of IL-13. In contrast, the expression of mIL-13R alpha 1 by Ba/F3 cells resulted in a sensitive proliferative response to IL-13. Consistent with its lower affinity for IL-13, IL-13R alpha 1.Fc was 100-fold less effective than IL-13R alpha 2.Fc in neutralizing IL-13 in vitro. These results show that mIL-13R alpha 2 and mIL-13R alpha 1 are not functionally equivalent and predict distinct roles for each polypeptide in IL-13R complex formation and in the modulation of IL-13 signal transduction.
Corepressor-Dependent Silencing of Chromosomal Regions Encoding Neuronal Genes (2002)

The molecular mechanisms by which central nervous system-specific genes are expressed only in the nervous system and repressed in other tissues remain a central issue in developmental and regulatory biology. Here, we report that the zinc-finger gene-specific repressor element RE-1 silencing transcription factor/neuronal restricted silencing factor (REST/NRSF) can mediate extraneuronal restriction by imposing either active repression via histone deacetylase recruitment or long-term gene silencing using a distinct functional complex. Silencing of neuronal-specific genes requires the recruitment of an associated corepressor, CoREST, that serves as a functional molecular beacon for the recruitment of molecular machinery that imposes silencing across a chromosomal interval, including transcriptional units that do not themselves contain REST/NRSF response elements.
Protein expression in a transformed trabecular meshwork cell line: proteome analysis. (2006)

Proteomic analysis of a transformed human TM cell line has been initiated combining preparative two-dimensional PAGE separation, LC/MS/MS analysis of major proteins, and bioinformatic cataloging of the data. Further investigation of data from the transformed cell strain will be used in a comparative fashion for spot identification of analytical proteomic gels of human TM tissue and cultured normal cells. These initial data will form the base from which the characterization of protein expression in the normal and glaucomatous TM can be accomplished.
Cytochrome P-450terp. Isolation and purification of the protein and cloning and sequencing of its operon. (1992)

Cytochromes P-450 are extremely important in the oxidative metabolism of a variety of endogenous and exogenous compounds in pro- and eukaryotic organisms. Progress in understanding the structure and mechanism of action of this superfamily of enzymes has been hampered by the properties of the eukaryotic enzymes and the availability of only one well-characterized prokaryotic enzyme as a model. We report here the isolation of a Pseudomonas species which will utilize a monoterpene natural product, alpha-terpineol, as its sole source of carbon and energy. Approximately 1% of the soluble protein in the cell-free extract is a novel cytochrome P-450 (P-450terp). This enzyme and its associated iron sulfur protein electron carrier (terpredoxin) have been purified to homogeneity and their NH2-terminal amino acid sequences determined. The amino acid sequences of six tryptic peptide fragments of cytochrome P-450terp have also been determined. This sequence information was used to clone the gene encoding cytochrome P-450terp. Three clones representing approximately 8 kilobase pairs of unique sequences were selected and sequenced. Five non-overlapping open reading frames (ORFs) were found in the sequences, and the translated sequences were used to search the Protein Identification Resource for comparable proteins. The ORFs were identified as: 1) an alcohol dehydrogenase, 2) an aldehyde dehydrogenase, 3) cytochrome P-450terp, 4) terpredoxin reductase, and 5) terpredoxin. The identification of both the cytochrome P-450terp and terpredoxin DNA sequence was confirmed by the presence of each of the corresponding amino acid sequences found in the purified proteins. The five ORFs were bounded on both the 5' and 3' ends by consensus factor-independent terminator sequences. A consensus promoter sequence was found immediately 5' to the first ORF. These results indicate that we have sequenced the complete terp operon. Comparison of the amino acid sequence of cytochrome P-450terp to that of all other cytochromes P-450 has shown that it is the first member of the gene family CYP108. Preliminary characterization of the chemical and physical properties and the preparation of crystals of this new cytochrome P-450, suitable for x-ray diffraction analysis, indicate that it will be useful in comparison studies with other members of this class of proteins.