gebhart/patrepeval huggingface dataset:
Coactivation with anti-CD28 monoclonal antibody enhances anti-CD3 monoclonal antibody-induced proliferation and IL-2 synthesis in T cells from autologous bone marrow transplant recipients. (1993)

Recent studies show that costimulation of T cells with anti-CD28 Mab (anti-CD28) enhances anti-CD3 Mab (anti-CD3)-induced proliferative responses and cytokine production. This study determines if coactivation with anti-CD3 and anti-CD28 corrects defects in proliferation and IL-2 secretion in peripheral blood lymphocytes (PBL) from bone marrow transplant (BMT) recipients. PBL or T cells from 5 of 16 autologous and 5 of 22 allogeneic recipients increased their anti-CD3-induced proliferation responses by > 50% after coactivation. In short-term (< 180 days after BMT) autologous recipients, the group mean response increased after anti-CD3 activation from 62,900 to 97,800 cpm after coactivation. In long-term (> 180 day after BMT) autologous recipients, the group mean response after anti-CD3 activation increased from 62,600 to 78,400 cpm after coactivation. The long-term autologous recipient group had costimulated responses from PBL that were significantly higher than the paired anti-CD3-induced responses (p < 0.01); in contrast, such differences were not seen in allogeneic recipient groups. After anti-CD3 stimulation, the mean response of 88,000 cpm for PBL from short-term allogeneic recipients and the mean response of 83,600 cpm for PBL from long-term allogeneic recipients were higher than those in PBL from autologous recipients were higher than those in PBL from autologous recipient groups. The amount of IL-2 secreted by T cells from three autologous and three allogeneic recipients was enhanced 0.9-25-fold by coactivation. Coactivation of PBL from selected recipients increased proliferation into the normal range and increased IL-2 secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Factors associated with the onset and remission of chronic daily headache in a population-based study (2003)

The etiology and prognosis of chronic daily headache (CDH) are not well understood. The aim of this study is to describe factors that predict CDH onset or remission in an adult population. Potential cases (180+ headaches per year, n=1134) and controls (two to 104 headaches per year, n=798) were interviewed two times over an average 11 months of follow-up. Factors associated with CDH prevalence at baseline were evaluated. The incidence of CDH and risk factors for onset were assessed in controls whose headache frequency increased to 180+ per year at follow-up. Prognostic factors were assessed in CDH cases whose headache frequency fell at follow-up. CDH was more common in women, in whites, and those of less education. CDH cases were more likely to be previously married (divorced, widowed, separated), obese, and report a physician diagnosis of diabetes or arthritis. At follow-up, 3% of the controls reported 180 or more headaches per year. Obesity and baseline headache frequency were significantly associated with new onset CDH. In CDH cases, the projected 1-year remission rate to less than one headache per week was 14% and to less than 180 headaches per year was 57%. A better prognosis was associated with higher education, non-white race, being married, and with diagnosed diabetes. Individuals with less than a high-school education, whites, and those who were previously married had a higher risk of CDH at baseline and reduced likelihood of remission at follow-up. New onset CDH was associated with baseline headache frequency and obesity.
NOVEL APPROACHES TO Topical Psoriasis Therapy. (2016)

Topical corticosteroids are the cornerstone of treatment for the majority of psoriasis patients. However, potential side effects of topical corticosteroids (i.e., cutaneous atrophy, telangiectasias, hypothalamic-pituitary axis suppression), coupled with the complex pathophysiology of psoriasis and the individual needs/preferences of psoriasis patients, represent a few of the limitations associated with topical corticosteroid monotherapy. While the combination of some agents with varying mechanisms of action has proven to be an effective strategy for improving efficacy and reducing concomitant drug application, others have displayed less efficacy, harm, and/or reduced cost-effectiveness. The purpose of this article is to review novel topical therapeutic combinations for the management of psoriasis and explore the role compounding pharmacies can have in providing healthcare providers and patients with effective and affordable alternative psoriasis therapies.
Generation and identification of recombinant adenovirus by liposome-mediated transfection and PCR analysis. (1993)

A simplified method for generating recombinant adenovirus was developed by using liposome-mediated co-transfection and by directly observing for the cytopathic effect caused by recombinant adenovirus in transfected 293 cells. This approach avoided difficulties associated with calcium-phosphate precipitation and agarose overlays for plaque assays. The ease of generating recombinant adenovirus was considerably improved. Analysis by PCR of DNA samples from the supernatant of the cell cultures with the cytopathic effect was also developed, which made identification of any newly generated recombinant virus rapid and specific.
A novel type of phospholipase A2 inhibitor, thielocin A1.BETA., and mechanism of action. (1992)

Thielocin A1 beta, a novel phospholipase A2 inhibitor, was isolated from Thielavia terricola RF-143. It inhibited various phospholipase A2s in a dose-dependent manner. Among these, group II phospholipase A2 from rat was most sensitive to thielocin A1 beta (IC50 = 0.0033 microM). The inhibition of phospholipase A2 by thielocin A1 beta was independent of Ca2+ and substrate concentration. In addition, the inhibition of rat group II phospholipase A2 was noncompetitive (Ki = 0.0068 microM) and reversible. Furthermore, thielocin A1 beta quenched the relative fluorescent intensity of Naja naja venom phospholipase A2 and in a dose-dependent manner; 50% quench was noted with a molar ratio of thielocin A1 beta/enzyme of 2.2. These observations indicated that inhibition of phospholipase A2 by thielocin A1 beta may result from direct interaction with the enzyme.
Mechanisms of fibrin polymerization and clinical implications (2013)

Research on all stages of fibrin polymerization, using a variety of approaches including naturally occurring and recombinant variants of fibrinogen, x-ray crystallography, electron and light microscopy, and other biophysical approaches, has revealed aspects of the molecular mechanisms involved. The ordered sequence of fibrinopeptide release is essential for the knob-hole interactions that initiate oligomer formation and the subsequent formation of 2-stranded protofibrils. Calcium ions bound both strongly and weakly to fibrin(ogen) have been localized, and some aspects of their roles are beginning to be discovered. Much less is known about the mechanisms of the lateral aggregation of protofibrils and the subsequent branching to yield a 3-dimensional network, although the αC region and B:b knob-hole binding seem to enhance lateral aggregation. Much information now exists about variations in clot structure and properties because of genetic and acquired molecular variants, environmental factors, effects of various intravascular and extravascular cells, hydrodynamic flow, and some functional consequences. The mechanical and chemical stability of clots and thrombi are affected by both the structure of the fibrin network and cross-linking by plasma transglutaminase. There are important clinical consequences to all of these new findings that are relevant for the pathogenesis of diseases, prophylaxis, diagnosis, and treatment.
Multidimensional binary search trees used for associative searching (1975)

This paper develops the multidimensional binary search tree (or k -d tree, where k is the dimensionality of the search space) as a data structure for storage of information to be retrieved by associative searches. The k -d tree is defined and examples are given. It is shown to be quite efficient in its storage requirements. A significant advantage of this structure is that a single data structure can handle many types of queries very efficiently. Various utility algorithms are developed; their proven average running times in an n record file are: insertion, O (log n ); deletion of the root, O ( n ( k -1)/ k ); deletion of a random node, O (log n ); and optimization (guarantees logarithmic performance of searches), O ( n log n ). Search algorithms are given for partial match queries with t keys specified [proven maximum running time of O ( n ( k - t )/ k )] and for nearest neighbor queries [empirically observed average running time of O (log n ).] These performances far surpass the best currently known algorithms for these tasks. An algorithm is presented to handle any general intersection query. The main focus of this paper is theoretical. It is felt, however, that k -d trees could be quite useful in many applications, and examples of potential uses are given.
A Survey of Mobile Computing Technologies and Applications (1995)

This document presents the results of a survey we did on mobile computing technologies and applications. Based on the results of this survey, we identify major academic and non--academic research institutions in the area of mobile computing, as well as the most challenging issues that need to be addressed to fully realize the dream of truly mobile computing. This document is organized as follows: Section 2 provides information on the survey methodology used and summarizes the results. Section 3 provides brief summaries of most of the papers identified by this survey. Section 4 provides a list of uniform resource locators (URLs) that constitutes a webliography of references, a World Wide Web list of sites that contain (hypertext) information on mobile computing. A comprehensive bibliography is given in the references section. 2 The Survey
Manual of Clinical Microbiology (1991)

General Issues in Clinical Microbiology Diagnostic Technologies in Clinical Microbiology Nosocomial and Community Infections: the Role of the Clinical Microbiology Laboratory Bacteria Fungi Parasites Viruses Rickettsiae and Chlamydiae Antimicrobial Agents and Susceptibility Tests Quality Control, Media, Reagents and Stains.
Antiadipogenic Effects of the Mineralocorticoid Receptor Antagonist Drospirenone: Potential Implications for the Treatment of Metabolic Syndrome (2010)

The mineralocorticoid receptor (MR) mediates aldosterone- and glucocorticoid-induced adipocyte differentiation. Drospirenone (DRSP) is a potent synthetic antimineralocorticoid with progestogenic and antiandrogenic properties, which is widely used for contraception and hormone replacement therapy. We investigated its potential role on adipocyte differentiation. The effects of DRSP were studied in murine preadipocyte cell lines and primary cultures of human preadipocytes. Differentiation markers and mechanisms underlying phenotypic variations in response to DRSP were explored. Early exposure to DRSP during differentiation led to a marked dose-dependent inhibition of adipose differentiation and triglyceride accumulation in 3T3-L1 and 3T3-F442A cells. DRSP also markedly inhibited adipose conversion of human primary preadipocytes derived from visceral (mesenteric and epicardial) and subcutaneous fat. This effect was MR-dependent and did not involve the glucocorticoid, androgen, or progesterone receptors. DRSP inhibited clonal expansion of preadipocytes and decreased expression of PPARγ, a key transcriptional mediator of adipogenesis, but had no effect on lipolysis, glucose uptake, and PPARγ binding to its ligands. DRSP exerts a potent antiadipogenic effect that is related to an alteration of the transcriptional control of adipogenesis via an antagonistic effect on the MR. Selective MR blockade therefore has promise as a novel therapeutic option for the control of excessive adipose tissue deposition and its related metabolic complications.
Philosophical Reflections on the Status of Cognitive Science (2000)

Philosophy of mind has been one of the most active and productive fields of philosophy during the past three decades. This has been due, in part, to the explosive growth of the cognitive sciences-cognitive psychology, cognitive neuroscience, psycholinguistics, AI, and related fields. And there have been fruitful exchanges between philosophers and the scientists who are interested in the philosophical foundations of these burgeoning fields. The philosophical mind-body problem is that of understanding and elucidating the relationship between mentality and its physical basis-how perceptions, sensations, thoughts, memory, reasoning, and the like are related to their biological/neural substrates. Among the many issues that arise in this connection, two have been especially prominent of late: consciousness and mental causation. The problem of consciousness concerns whether and how the phenomenon of consciousness can be physically explained
Evaluation of Three Rubella Vaccines in Adult Women (1970)

A currently licensed rubella vaccine, HPV 77, produces arthralgia at high frequency in adult women. Thirty-nine susceptible adult women, ages 18 to 37 years, were inoculated with Cendehill, Benoit B, and Benoit C rubella vaccine strains and evaluated clinically and serologically. Benoit B produced rubellalike disease including polyarthralgia in five of seven women which, in one case, was of five months' duration. The postvaccination course of Benoit C vaccine was benign in all 11 subjects; only two of 28 Cendehill vaccinees had mild, transient arthralgia. Postvaccination hemagglutination-inhibition antibody to levels greater than 1:10 developed in all susceptible subjects. Benoit B vaccinees had the highest titers, Cendehill, intermediate values, while Benoit C titers were rather low. Cendehill and perhaps Benoit C strains appear to be immunogenic and clinically acceptable in adult women.
Genes involved in organ separation in Arabidopsis: an analysis of the cup-shaped cotyledon mutant. (1997)

Mutations in CUC1 and CUC2 (for CUP-SHAPED COTYLEDON), which are newly identified genes of Arabidopsis, caused defects in the separation of cotyledons (embryonic organs), sepals, and stamens (floral organs) as well as in the formation of shoot apical meristems. These defects were most apparent in the double mutant. Phenotypes of the mutants suggest a common mechanism for separating adjacent organs within the same whorl in both embryos and flowers. We cloned the CUC2 gene and found that the encoded protein was homologous to the petunia NO APICAL MERISTEM (NAM) protein, which is thought to act in the development of embryos and flowers.
Long-Term Outcomes with Drug-Eluting Stents versus Bare-Metal Stents in Sweden (2007)

Drug-eluting stents were associated with an increased rate of death, as compared with bare-metal stents. This trend appeared after 6 months, when the risk of death was 0.5 percentage point higher and a composite of death or myocardial infarction was 0.5 to 1.0 percentage point higher per year. The long-term safety of drug-eluting stents needs to be ascertained in large, randomized trials.
Weight loss for primary prevention of stroke in people with overweight or obesity (2006)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of weight reduction in patients with overweight and obesity on stroke incidence.
Protease and Protease-Activated Receptor-2 Signaling in the Pathogenesis of Atopic Dermatitis (2010)

Proteases in the skin are essential to epidermal permeability barrier homeostasis. In addition to their direct proteolytic effects, certain proteases signal to cells by activating protease-activated receptors (PARs), the G-protein-coupled receptors. The expression of functional PAR-2 on human skin and its role in inflammation, pruritus, and skin barrier homeostasis have been demonstrated. Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by genetic barrier defects and allergic inflammation, which is sustained by gene-environmental interactions. Recent studies have revealed aberrant expression and activation of serine proteases and PAR-2 in the lesional skin of AD patients. The imbalance between proteases and protease inhibitors associated with genetic defects in the protease/protease inhibitor encoding genes, increase in skin surface pH, and exposure to proteolytically active allergens contribute to this aberrant protease/ PAR-2 signaling in AD. The increased protease activity in AD leads to abnormal desquamation, degradation of lipid-processing enzymes and antimicrobial peptides, and activation of primary cytokines, thereby leading to permeability barrier dysfunction, inflammation, and defects in the antimicrobial barrier. Moreover, up-regulated proteases stimulate PAR-2 in lesional skin of AD and lead to the production of cytokines and chemokines involved in inflammation and immune responses, itching sensation, and sustained epidermal barrier perturbation with easier allergen penetration. In addition, PAR-2 is an important sensor for exogenous danger molecules, such as exogenous proteases from various allergens, and plays an important role in AD pathogenesis. Together, these findings suggest that protease activity or PAR-2 may be a future target for therapeutic intervention for the treatment of AD.
Antiviral Drug Therapy of Filovirus Infections: S‐Adenosylhomocysteine Hydrolase Inhibitors Inhibit Ebola Virus In Vitro and in a Lethal Mouse Model (1999)

Ebola (subtype Zaire) viral replication was inhibited in vitro by a series of nine nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase, an important target for antiviral drug development. Adult BALB/c mice lethally infected with mouse-adapted Ebola virus die 5-7 days after infection. Treatment initiated on day 0 or 1 resulted in dose-dependent protection, with mortality completely prevented at doses > or =0.7 mg/kg every 8 h. There was significant protection (90%) when treatment was begun on day 2, at which time, the liver had an average titer of 3 x 10(5) pfu/g virus and the spleen had 2 x 10(6) pfu/g. Treatment with 2.2 mg/kg initiated on day 3, when the liver had an average titer of 2 x 10(7) pfu/g virus and the spleen had 2 x 10(8) pfu/g, resulted in 40% survival. As reported here, Carbocyclic 3-deazaadenosine is the first compound demonstrated to cure animals from this otherwise lethal Ebola virus infection.
Hyaluronidase Levels in Urine From Wilms' Tumor Patients (1991)

The pathophysiology of Wilms' tumor is associated with major alterations in hyaluronic acid metabolism. Elevated levels of both hyaluronic acid and a hyaluronic acid-stimulating activity occur in the urine and serum of patients with this tumor. In the current study, we describe elevated levels of urinary hyaluronidase in five patients with Wilms' tumor. Following surgical removal of the tumor, enzyme levels decreased toward normal. Characterization of enzyme activity indicates that hyaluronidase may be produced by the tumor itself. Alternatively, normal renal tissue may also be producing enzyme in a compensatory response to the elevated hyaluronic acid levels in these patients. We suggest that urinary hyaluronidase can be used as an additional marker for Wilms' tumor.
Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy (1995)

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder with a high spontaneous mutation rate and no effective treatment, hence development of genetic based therapies is an important goal. We report that expression of a recombinant human minidystrophin cDNA, compatible with current viral vectors, can significantly reduce the myopathic phenotype in transgenic mdx mice, even when expressed at only 20-30% of endogenous dystrophin levels at the sarcolemma. To the extent that data obtained in mouse studies are applicable to DMD, the virtual elimination of morphological and biochemical abnormalities in the mdx mouse supports the use of this cDNA in somatic gene therapy protocols for DMD.
Heparinase I from Flavobacterium heparinum. Identification of a Critical Histidine Residue Essential for Catalysis As Probed by Chemical Modification and Site-Directed Mutagenesis (1996)

We recently identified cysteine-135 as an important amino acid for heparinase I (EC 4.2.2.7) activity. In this study, we have identified a second residue critical for enzymatic activity. We observe concentration-dependent inactivation of heparinase I in the presence of reversible histidine-modifying diethyl pyrocarbonate (DEPC); 0.3 mM DEPC results in 95% of heparinase I inactivation in less than 3 min, and as low as 10 microM DEPC results in a 85% loss of heparinase I activity in 15 min. Heparinase I activity is restored following hydroxylamine treatment. This, along with other experiments, strongly suggests that the inactivation of heparinase I by DEPC is specific for histidine residues. Chemical modification, under nondenaturing conditions, of the histidines using nonradiolabeled and [14C]DEPC indicates that between one and two histidine residues are modified. Chemical modification of the surface-accessible histidines, in the presence and absence of heparin, suggests that the histidine(s) lie(s) in or near the active site of heparinase I. The wild-type heparinase I has four histidine residues; site-directed mutagenesis of H129A, H165A, and H339A did not affect enzyme activity and the kinetic parameters, suggesting that these residues are not essential for heparinase I activity. However, H203A inactivates heparinase I while a H203D mutant has residual activity, indicating a role of this residue in catalysis. We propose that histidine-203, contained in the heparin binding site, is immediately adjacent to cysteine-135, and these residues together form the catalytic domain of heparinase I.
2: 3-Dihydro-3-oxobenz-1: 4-oxazines (1955)

J. D. Loudon and J. Ogg, J. Chem. Soc., 1955, 739 DOI: 10.1039/JR9550000739
C5a alters blood‐brain barrier integrity in experimental lupus (2010)

The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.