gebhart/patrepeval huggingface dataset:
Human IgA nephritis: immunocytochemical evidence of a chronic inflammatory proliferative disorder. (1995)

This overview summarizes recent information concerning the biopathology of mesangial cell proliferation and matrix expansion which constitute fundamental features in human IgA nephritis. The currently available knowledge, mainly stemming for immunohistochemical observation of human materials, experimental investigations with laboratory animals, and mesangial cell culture studies, emphasizes the importance of cell to cell, cell to soluble factors, and cell to matrix interactions. Mesangial cells, activated by cytokines and growth factors, express adhesion molecules, stimulate proliferation both of themselves and neighbouring cells, and synthesize extracellular matrix. Matrix components, in turn, may influence the behaviour and proliferation activity of mesangial cells, or act as a receptor or reservoir for growth factors. Expression of protooncogenes, regulating cell proliferation and apoptosis, by glomerular cells could be associated with persistent cell replication and chronic tissue damage. These disease processes seem to be common to a group of diseases termed chronic inflammatory proliferative disorders.
Combined direct current and high frequency nerve block for elimination of the onset response (2009)

Nerve conduction in peripheral mammalian nerves can be blocked by high frequency alternating current (HFAC) waveforms. However, one of the disadvantages of HFAC block is that it produces an intense burst of firing in the nerve when the HFAC is first turned on. This is a significant obstacle to the clinical implementation of HFAC block. In this paper we present a method to produce HFAC block without the onset response, using a combination of direct current (DC) and HFAC block. This method was experimentally evaluated in an in-vivo mammalian model. Successful no-onset HFAC block was obtained using a DC block of 200 microA and an HFAC block of 30 kHz at 10 Vp-p. This may allow HFAC block to be used in clinical applications for pain relief.
Mechanism of Redox-mediated Guanine Nucleotide Exchange on Redox-active Rho GTPases (2005)

Rho GTPases regulate multiple cellular processes including actin cytoskeletal rearrangements, transcriptional regulation, and oxidant production. The studies described herein demonstrate that small molecule redox agents, in addition to protein regulatory factors, can regulate the activity of redox-active Rho GTPases. A novel (GXXXXGK(S/T)C) motif, conserved in a number of Rho GTPases, appears critical for redox-mediated guanine nucleotide dissociation in vitro. A detailed molecular mechanism for redox regulation of GXXXXGK(S/T)C motif-containing Rho GTPases is proposed.
Complications and Symptoms in Disposable Extended Wear Lenses Compared with Conventional Soft Daily Wear and Soft Extended Wear Lenses (1993)

We conducted a historical cohort study of 2,433 cosmetic contact lens wearers (1,055 conventional [non-disposable] daily wear lens users, 905 disposable extended wear lens users, and 473 conventional extended wear lens users) in order to estimate the rates of occurrence of complications and symptoms among disposable extended wear contact lens users and compare these rates with those for conventional soft daily wear users and conventional soft extended wear users. Data were abstracted from the office records of eight eye care practitioners for the period February 1987 through April 1989. The prevalence of all complications for disposable extended wear lens users was not significantly different from the prevalence for conventional daily wear lens users but was significantly lower than the prevalence for conventional extended wear lens users. The incidence of ulcers among disposable extended wear lens users did not differ significantly from the incidence found with conventional extended wear, but was significantly higher than the rate for conventional daily wear. Disposable extended wear lenses, in contrast to conventional extended wear lenses, may be more strongly associated with benign peripheral infiltrates than with the more serious central ulcers. Disposable extended wear lens users reported symptoms less frequently at routine scheduled visits than both conventional daily wear and conventional extended wear users and had a lower rate of unscheduled visits for complications and symptoms.
Cytokines and Chemokines as Biomarkers of Community-Acquired Bacterial Infection (2013)

Routinely used biomarkers of bacterial etiology of infection, such as C-reactive protein and procalcitonin, have limited usefulness for evaluation of infections since their expression is enhanced by a number of different conditions. Therefore, several inflammatory cytokines and chemokines were analyzed with sera from patients hospitalized for moderate bacterial and viral infectious diseases. In total, 57 subjects were enrolled: 21 patients with community-acquired bacterial infections, 26 patients with viral infections, and 10 healthy subjects (control cohorts). The laboratory analyses were performed using Luminex technology, and the following molecules were examined: IL-1Ra, IL-2, IL-4, IL-6, IL-8, TNF- α , INF- γ , MIP-1 β , and MCP-1. Bacterial etiology of infection was associated with significantly (P < 0.001) elevated serum concentrations of IL-1Ra, IL-2, IL-6, and TNF- α in comparison to levels observed in the sera of patients with viral infections. In the patients with bacterial infections, IL-1Ra and IL-8 demonstrated positive correlation with C-reactive protein, whereas, IL-1Ra, TNF- α , and MCP-1 correlated with procalcitonin. Furthermore, elevated levels of IL-1Ra, IL-6, and TNF- α decreased within 3 days of antibiotic therapy to levels observed in control subjects. The results show IL-1Ra as a potential useful biomarker of community-acquired bacterial infection.
Broad-Host-Range Yersinia Phage PY100: Genome Sequence, Proteome Analysis of Virions, and DNA Packaging Strategy (2007)

PY100 is a lytic bacteriophage with a broad host range within the genus Yersinia. The phage forms plaques on strains of the three human pathogenic species Yersinia enterocolitica, Y. pseudotuberculosis, and Y. pestis at 37 degrees C. PY100 was isolated from farm manure and intended to be used in phage therapy trials. PY100 has an icosahedral capsid containing double-stranded DNA and a contractile tail. The genome consists of 50,291 bp and is predicted to contain 93 open reading frames (ORFs). PY100 gene products were found to be homologous to the capsid proteins and proteins involved in DNA metabolism of the enterobacterial phage T1; PY100 tail proteins possess homologies to putative tail proteins of phage AaPhi23 of Actinobacillus actinomycetemcomitans. In a proteome analysis of virion particles, 15 proteins of the head and tail structures were identified by mass spectrometry. The putative gene product of ORF2 of PY100 shows significant homology to the gene 3 product (small terminase subunit) of Salmonella phage P22 that is involved in packaging of the concatemeric phage DNA. The packaging mechanism of PY100 was analyzed by hybridization and sequence analysis of DNA isolated from virion particles. Newly replicated PY100 DNA is cut initially at a pac recognition site, which is located in the coding region of ORF2.
c-Jun NH2-Terminal Kinase Activating Kinase 1/Mitogen-Activated Protein Kinase Kinase 4–Mediated Inhibition of SKOV3ip.1 Ovarian Cancer Metastasis Involves Growth Arrest and p21 Up-regulation (2008)

In many patients without clinical metastases, cancer cells have already escaped from the primary tumor and entered a distant organ. A long-standing question in metastasis research is why some disseminated cancer cells fail to complete steps of metastatic colonization for extended periods of time. Our laboratory identified c-Jun NH(2)-terminal kinase activating kinase 1/mitogen-activated protein kinase kinase 4 (JNKK1/MKK4) as a metastasis suppressor protein in a mouse xenograft model of experimental i.p. ovarian cancer metastasis. In this model, expression of JNKK1/MKK4 via activation of p38 delays formation of >or=1-mm implants and prolongs animal survival. Here, we elucidate the time course of this delay as well as the biological mechanisms underpinning it. Using the Gompertz function to model the net accumulation of experimental omental metastases, we show that MKK4-expressing implants arise, on average, 30 days later than controls. Quantitative real-time PCR shows that MKK4 expression does not have a substantial effect on the number of cancer cells initially adhering to the omentum, and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling analysis shows that there is no increase in apoptosis in these cells. Instead, immunohistochemical quantitation of cell cycle proteins reveals that MKK4-expressing cells fail to proliferate once they reach the omentum and up-regulate p21, a cell cycle inhibitor. Consistent with the time course data, in vitro kinase assays and in vivo passaging of cell lines derived from macroscopic metastases show that the eventual outgrowth of MKK4-expressing cells is not due to a discrete selection event. Rather, the population of MKK4-expressing cells eventually uniformly adapts to the consequences of up-regulated MKK4 signaling.
N -Acetylaspartate and N -acetylaspartylglutamate (2008)

N -Acetylaspartate (NAA) and its derivative, N -acetylaspartylglutamate (NAAG), are synthesized in neurons and present in very high concentrations in the CNS. NAA is a marker of the functional integrity of neuronal mitochondrial metabolism and may be critical for myelinogenesis,1 whereas NAAG modulates glutamatergic transmission and may have a role in neuroprotection and synaptic plasticity.2 Regional reduction of NAA levels measured by magnetic resonance spectroscopy (MRS) has been used as a marker of neuronal or axonal loss in several neurologic disorders, including traumatic brain injury, stroke, epilepsy, and multiple sclerosis, but may also reflect reversible metabolic impairment. Elevation of NAA levels is a hallmark of Canavan disease, a severe demyelinating disorder of infancy.1 Inhibitors of NAAG peptidase provide neuroprotection in experimental models of stroke, head trauma, and amyotrophic lateral sclerosis (ALS), presumably by increasing endogenous NAAG signaling.2 Thus, elucidation of the neurobiology of NAA and NAAG provides insight into the role of these molecules in the pathophysiology of several neurologic disorders and their potential as a therapeutic target for these conditions.

NAA and NAAG participate in important mechanisms of signaling among neurons and glial cells (figure).





Figure Interactions among neurons and glial cells mediated by N -acetylaspartate (NAA) and N -acetylaspartylglutamate (NAAG)

In neurons, NAA is synthesized in the mitochondria and is then transported to oligodendrocytes, when it is metabolized by the aspartoacylase (ASPA) to acetate. Acetate serves as a precursor for synthesis of myelin lipids. In neurons, NAA is combined to glutamate to produce NAAG, which is released from synaptic vesicles and acts as a cotransmitter with several other neurotransmitters, including l-glutamate. NAAG, acting via presynaptic type 3 metabotropic glutamate receptors (mGluR3), blocks presynaptic calcium (Ca2+) channels, thus inhibiting glutamate release. NAAG may also bind to N -methyl-d-aspartate receptors, blocking their function. NAAG, …
Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for Bone Morphogenetic Protein-2A (BMP-2A) (1990)

Bone morphogenetic protein-2A (BMP-2A) is a member of the transforming growth factor beta (TGF beta) gene family that has been implicated in cartilage and bone formation. Here we use in situ hybridization to show that BMP-2A RNA is expressed in a variety of embryonic epithelial and mesenchymal tissues outside of the developing skeletal system, including cell populations known to play important roles in morphogenesis. Thus, high levels of transcripts are found in developing limb buds (ventral ectoderm and apical ectodermal ridge), heart (myocardium of the atrioventricular canal), whisker follicles (ectodermal placodes, hair matrix and precortex cells), tooth buds (epithelial buds, dental papilla and odontoblasts), and craniofacial mesenchyme, as well as a number of other sites. The expression patterns of BMP-2A are different from those of TGF beta-1, -2 and -3, and this is illustrated in detail in the developing whisker follicles. These results suggest that BMP-2A plays multiple roles in morphogenesis and pattern formation in the vertebrate embryo.
Chemical modification of titanium surfaces for covalent attachment of biological molecules (1998)

The surface of implantable biomaterials is in direct contact with the host tissue and plays a critical role in determining biocompatibility. In order to improve the integration of implants, it is desirable to control interfacial reactions such that nonspecific adsorption of proteins is minimized and tissue-healing phenomena can be controlled. In this regard, our goal has been do develop a method to functionalize oxidized titanium surfaces by the covalent immobilization of bioactive organic molecules. Titanium first was chemically treated with a mixture of sulfuric acid and hydrogen peroxide to eliminate surface contaminants and to produce a consistent and reproducible titanium oxide surface layer. An intermediary aminoalkylsilane spacer molecule was then covalently linked to the oxide layer, followed by the covalent binding of either alkaline phosphatase or albumin to the free terminal NH2 groups using glutaraldehyde as a coupling agent. Surface analyses following coating procedures consisted of X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Enzymatic activity of coupled alkaline phosphatase was assayed colorimetrically, and surface coverage by bound albumin was evaluated by SEM visualization of colloidal gold immunolabeling. Our results indicate that the linkage of the aminoalkylsilane to the oxidized surface is stable and that bound proteins such alkaline phosphatase and albumin retain their enzymatic activity and antigenicity, respectively. The density of immunolabeling for albumin suggests that the binding and surface coverage obtained is in excess of what would be expected for inducing biological activity. In conclusion, this method offers the possibility of covalently linking selected molecules with known biological activity to oxidized titanium surfaces in order to guide and promote the tissue healing that occurs during implant integration in bone and soft tissues.
Diagnosis and Management of Bacterial Vaginosis and Other Types of Abnormal Vaginal Bacterial Flora: A Review (2010)

After completion of this educational activity, the participant should be better able to analyze bacterial vaginosis clinically, formulate an oral antibiotic treatment regimen for bacterial vaginosis and use vaginal treatments for bacterial vaginosis.
Rational design of quinazoline-based irreversible inhibitors of human erythrocyte purine nucleoside phosphorylase (1991)

Described herein is the rational design of irreversible inhibitors of human erythrocyte purine nucleoside phosphorylase (PNPase). Inhibitor design started with the observation that the amino group of 8-aminoquinazolin-4(3H)-one interacts with enzyme-bound phosphate. This observation correctly predicted that the 5,8-dione (quinone) and 5,8-dihydroxy (hydroquinone) derivatives of quinazolin-4(3H)-ones would enter the active site. The amine-phosphate interaction also served to confirm that a quinazolin-4(3H)-one binds in the PNPase active sites like a purine substrate. From models of the PNPase active site it was possible to design quinazoline-based quinones that undergo a reductive-addition reaction with an active-site glutamate residue. The best inhibitor studied, 2-(chloromethyl)quinazoline-4,5,8(3H)-trione, rapidly inactivates PNPase by a first-order process with an inhibitor to enzyme stoichiometry of 150. The active-site hydroquinone adduct of this inhibitor eliminates a leaving group to afford a quinone methide species positioned to alkylate another active-site glutamate residue. Thus, this inhibitor is designed to cross-link the PNPase active site by reductive addition followed by the generation of an alkylating quinone methide species.
Synthesis of Fe Oxide Core/Au Shell Nanoparticles by Iterative Hydroxylamine Seeding (2004)

Water-soluble, Au-coated magnetic Fe oxide nanoparticles with diameters ∼60 nm were synthesized by the reduction of Au3+ onto the surfaces of ∼9 nm diameter particles consisting of either γ-Fe2O3 or partially oxidized Fe3O4 via iterative hydroxylamine seeding. The morphology and optical properties of the core/shell particles are dependent on the quantity of deposited Au, while the magnetic properties remain largely independent of Au addition. The Au-coated particles exhibit a surface plasmon resonance peak that blue-shifts from 570 to 525 nm with increasing Au deposition. SQUID magnetometry reveals that particle magnetic properties are not affected by the overlayer of a moderately thick Au shell.
The Genome Sequence of Yersinia pestis Bacteriophage φA1122 Reveals an Intimate History with the Coliphage T3 and T7 Genomes (2003)

The genome sequence of bacteriophage phiA1122 has been determined. phiA1122 grows on almost all isolates of Yersinia pestis and is used by the Centers for Disease Control and Prevention as a diagnostic agent for the causative agent of plague. phiA1122 is very closely related to coliphage T7; the two genomes are colinear, and the genome-wide level of nucleotide identity is about 89%. However, a quarter of the phiA1122 genome, one that includes about half of the morphogenetic and maturation functions, is significantly more closely related to coliphage T3 than to T7. It is proposed that the yersiniophage phiA1122 recombined with a close relative of the Y. enterocolitica phage phiYeO3-12 to yield progeny phages, one of which became the classic T3 coliphage of Demerec and Fano (M. Demerec and U. Fano, Genetics 30:119-136, 1945).
Sink- and vascular-associated sucrose synthase functions are encoded by different gene classes in potato. (1995)

Two differentially regulated classes of sucrose synthase genes, Sus3 and Sus4, were identified in potato. They cannot be classified as Sus1 and Sus2 types based on sequence homology and appear to have evolved after the divergence of the major families of dicotyledonous plants but before the divergence of tomato and potato. The potato sucrose synthase clones Sus3-65 and Sus4-16 share an 87% nucleotide identity in the coding regions, and both are interrupted by 13 introns, including a long leader intron. Potato Sus3 genes are expressed at the highest levels in stems and roots and appear to provide the vascular function of sucrose synthase. In contrast, Sus4 genes are expressed primarily in the storage and vascular tissue of tubers and appear to facilitate sink function. The genes are differentially regulated in root tips, with Sus3 expressed at high levels in the cell division zone and Sus4 expressed at high levels in the meristem and cap.
Skin decontamination of mustards and organophosphates: comparative efficiency of RSDL and Fuller's earth in domestic swine (2007)

Research in skin decontamination and therapy of chemical warfare agents has been a difficult problem due to the simultaneous requirement of rapid action and non-aggressive behaviour. The aim of this study was to compare the performance of two decontaminating systems: the Canadian Reactive Skin Decontaminant Lotion (RSDL) and the Fuller's Earth (FE). The experiment was conducted with domestic swine, as a good model for extrapolation to human skin. RSDL and FE were tested against sulphur mustard (SM), a powerful vesicant, and VX, a potent and persistent cholinesterase inhibitor. When used 5 min after contamination, the results clearly showed that both systems were active against SM (10.1 mg/cm(2)) and VX (0.06 mg/cm(2)). The potency of the RSDL/sponge was statistically better than FE against skin injury induced by SM, observed 3 days post-exposure. RSDL was rather more efficient than FE in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. Against a severe inhibition (67%) of plasmatic cholinesterases induced by VX poisoning, the potencies of the RSDL/sponge and FE were similar. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin.
Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice (2010)

The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate-nitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.
Fibroblast growth factor 21 night watch: advances and uncertainties in the field (2016)

Fibroblast growth factor (FGF) 21 belongs to a hormone-like subgroup within the FGF superfamily. The members of this subfamily, FGF19, FGF21 and FGF23, are characterized by their reduced binding affinity for heparin that enables them to be transported in the circulation and function in an endocrine manner. It is likely that FGF21 also acts in an autocrine and paracrine fashion, as multiple organs can produce this protein and its plasma concentration seems to be below the level necessary to induce a pharmacological effect. FGF21 signals via FGF receptors, but for efficient receptor engagement it requires a cofactor, membrane-spanning βKlotho (KLB). The regulation of glucose uptake in adipocytes was the initial biological activity ascribed to FGF21, but this hormone is now recognized to stimulate many other pathways in vitro and display multiple pharmacological effects in metabolically compromised animals and humans. Understanding of the precise physiology of FGF21 and its potential medicinal role has evolved exponentially over the last decade, yet numerous aspects remain to be defined and others are a source of debate. Here we provide a historical overview of the advances in FGF21 biology focusing on the uncertainties in the mechanism of action as well as the differing viewpoints relating to this intriguing protein.