gebhart/patrepeval huggingface dataset:
In vivo evidence of the role of α4β1‐VCAM‐1 interaction in sarcoma, but not in carcinoma extravasation (1994)

Tumor-cell invasion can occur via either lymphatics or blood vessels. When in the blood circulation, tumor cells have to adhere to endothelium lining the blood vessels before they can extravasate. Several families of adhesion molecules have been recognized: selectins and their oligosaccharide-containing ligands and integrins and their counter-receptors belonging to the immunoglobulin superfamily. Besides their essential role in leukocyte extravasation, these adhesion molecules have been proposed by vitro experiments to be involved in tumor-cell invasion by facilitating the adhesion of malignant cells to endothelium leading to extravasation and metastasis. We have previously shown that, in vitro, several sarcoma cell lines adhere strongly to cultured endothelial cells via alpha 4 beta 1-VCAM-1 interaction. Here we show that sarcoma cells, especially in the metastatic lesions, were strongly alpha 4 beta 1 positive but did not express alpha 4 beta 7, which is another receptor for VCAM-I. Furthermore, we demonstrate that the capillary endothelium within metastatic sarcoma lesions reacted strongly with anti-VCAM-I antibody and very often the alpha 4 beta 1-expressing sarcoma cells were localized in the close vicinity of VCAM-I-expressing vessels. As control material we analyzed carcinoma specimens, but could not detect any alpha 4-integrin expression on malignant cells even though the endothelial cells were often VCAM-I positive. These results suggest that carcinomas do not use alpha 4 beta 1-VCAM-I in extravasation and, taken together, provide circumstantial evidence that in vitro findings of alpha 4 beta1-VCAM-I-dependent sarcoma cell adhesion to endothelium can be extended to in vivo situations.
Essential Role for the Lectin Pathway in Collagen Antibody–Induced Arthritis Revealed through Use of Adenovirus Programming Complement Inhibitor MAp44 Expression (2014)

Previous studies using mannose-binding lectin (MBL) and complement C4-deficient mice have suggested that the lectin pathway (LP) is not required for the development of inflammatory arthritis in the collagen Ab-induced arthritis (CAIA) model. MBL, ficolins and collectin-11 are key LP pattern recognition molecules that associate with three serine proteases-MASP-1, MASP-2, and MASP-3-and with two MBL-associated proteins designated sMAP and MBL-associated protein of 44kDA (MAp44). Recent studies have shown that MAp44, an alternatively spliced product of the MASP-1/3 gene, is a competitive inhibitor of the binding of the recognition molecules to all three MASPs. In these studies, we examined the effect of treatment of mice with adenovirus (Ad) programmed to express human MAp44 (AdhMAp44) on the development of CAIA. AdhMAp44 and Ad programming GFP (AdGFP) expression were injected i.p. in C57BL/6 wild type mice prior to the induction of CAIA. AdhMAp44 significantly reduced the clinical disease activity (CDA) score by 81% compared with mice injected with AdGFP. Similarly, histopathologic injury scores for inflammation, pannus, cartilage and bone damage, as well as C3 deposition in the cartilage and synovium, were significantly reduced by AdhMAp44 pretreatment. Mice treated with AdmMAp44, programming expression of mouse MAp44, also showed significantly decreased CDA score and histopathologic injury scores. In addition, administration of AdhMAp44 significantly diminished the severity of Ross River virus-induced arthritis, an LP-dependent model. Our study provides conclusive evidence that an intact complement LP is essential to initiate CAIA, and that MAp44 may be an appropriate treatment for inflammatory arthritis.
PREFERENTIAL EXPRESSION OF CHEMOKINE RECEPTOR CXCR4 BY HIGHLY MALIGNANT HUMAN GLIOMAS AND ITS ASSOCIATION WITH POOR PATIENT SURVIVAL (2007)

The level of CXCR4 expression seems to correlate with the degree of malignancy of human gliomas and may contribute to their rapid growth.
Basic fibroblast growth factor increases the effects of endotoxin and interferon gamma on iNOS and mouse aortic endothelial cells (2007)

Inflammatory cytokines and bacterial products, such as interferon gamma (IFN) and endotoxin (LPS) promote endothelial dysfunction. They induce the expression of inducible NO synthase (iNOS), which may play a role in the pathogenesis of vascular diseases. Basic fibroblast growth factor (FGF2) is an angiogenic factor that appears to protect endothelial cells from different stresses. Here we evaluated the effect of FGF2 on endothelial cells treated with LPS and IFN. Murine aortic endothelial cells (MAEC) were treated with LPS, IFN, FGF2 and an inhibitor of NO synthase, L‐NAME. The effect of treatment volume on iNOS induction was also determined. iNOS mRNA and protein were measured by RT‐PCR and western blotting. Cell injury was assessed by phase–contrast microscopy. LPS (10 ug/mL) plus IFN (20 ng/mL) synergistically increased iNOS mRNA and protein in MAEC, and minimal cell injury was detected. Remarkably, addition of FGF2 to LPS and IFN increased iNOS protein, in a dose‐dependent manner, up to another factor of 10. When the volume of treatment with FGF2, LPS and IFN was increased from 2 ml to 10 ml, this high induction of iNOS was reduced by 80%. The combination of FGF2 (5 ng/mL) with LPS and IFN caused cell loss (37‐fold increase in culture area devoid of cells) after 120 h, which was prevented by pre‐incubation with L‐NAME. The results suggest that, rather than protecting MAEC, FGF2 increased injury of cells treated with LPS and IFN. FGF2 also enhanced the induction of iNOS by LPS plus IFN, and facilitated cell injury by an iNOS‐dependent mechanism that may involve an autocrine factor.
Combination Therapy With Abciximab Reduces Angiographically Evident Thrombus in Acute Myocardial Infarction (2001)

Compared with thrombolytic monotherapy, combination therapy with abciximab reduces AET, which in turn is associated with reduced residual stenosis and improved ST-segment resolution in AMI. These data provide a pathophysiological link between platelet inhibition, reduced thrombus, and improvements in both epicardial and microvascular perfusion in AMI.
Covalent modification of guanine bases in double-stranded DNA. The 1.2-A Z-DNA structure of d(CGCGCG) in the presence of CuCl2. (1991)

We have solved the single crystal structure to 1.2-A resolution of the Z-DNA sequence d(CGCGCG) soaked with copper(II) chloride. This structure allows us to elucidate the structural properties of copper in a model that mimics a physiologically relevant environment. A copper(II) cation was observed to form a covalent coordinate bond to N-7 of each guanine base along the hexamer duplex. The occurrence of copper bound at each site was dependent on the exposure of the bases and the packing of the hexamers in the crystal. The copper at the highest occupied site was observed to form a regular octahedral complex, with four water ligands in the equatorial plane and a fifth water along with N-7 of the purine base at the axial positions. All other copper complexes appear to be variations of this structure. By using the octahedral complex as the prototype for copper(II) binding to guanine bases in the Z-DNA crystal, model structures were built showing that duplex B-DNA can accommodate octahedral copper(II) complexes at the guanine bases as well as copper complexes bridged at adjacent guanine residues by a reactive dioxygen species. The increased susceptibility to oxidative DNA cleavage induced by copper(II) ions in solution of the bases located 5' to one or more adjacent guanine residues can thus be explained in terms of the cation and DNA structures described by these models.
Web Programming (Unleashed) [Includes CD-Rom] (1996)

From the Publisher:
This comprehensive tomb explores all aspects of the latest technology craze-Internet programming. Programmers will turn to the proven expertise of the Unleashed series for accurate, day-and-date information on this hot new programming subject.
Gives timely, expert advice on ways to exploit the full potential of the Internet
CD-ROM includes complete source code for all applications in the book, additional programs with accompanying source code, and several Internet application resource tools.
The pharmacological chaperone 1‐deoxygalactonojirimycin increases α‐galactosidase A levels in Fabry patient cell lines (2009)

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding alpha-galactosidase A (alpha-Gal A), with consequent accumulation of its major glycosphingolipid substrate, globotriaosylceramide (GL-3). Over 500 Fabry mutations have been reported; approximately 60% are missense. The iminosugar 1-deoxygalactonojirimycin (DGJ, migalastat hydrochloride, AT1001) is a pharmacological chaperone that selectively binds alpha-Gal A, increasing physical stability, lysosomal trafficking, and cellular activity. To identify DGJ-responsive mutant forms of alpha-Gal A, the effect of DGJ incubation on alpha-Gal A levels was assessed in cultured lymphoblasts from males with Fabry disease representing 75 different missense mutations, one insertion, and one splice-site mutation. Baseline alpha-Gal A levels ranged from 0 to 52% of normal. Increases in alpha-Gal A levels (1.5- to 28-fold) after continuous DGJ incubation for 5 days were seen for 49 different missense mutant forms with varying EC(50) values (820 nmol/L to >1 mmol/L). Amino acid substitutions in responsive forms were located throughout both structural domains of the enzyme. Half of the missense mutant forms associated with classic (early-onset) Fabry disease and a majority (90%) associated with later-onset Fabry disease were responsive. In cultured fibroblasts from males with Fabry disease, the responses to DGJ were comparable to those of lymphoblasts with the same mutation. Importantly, elevated GL-3 levels in responsive Fabry fibroblasts were reduced after DGJ incubation, indicating that increased mutant alpha-Gal A levels can reduce accumulated substrate. These data indicate that DGJ merits further evaluation as a treatment for patients with Fabry disease with various missense mutations.
Nanosensor Detection of an Immunoregulatory Tryptophan Influx/Kynurenine Efflux Cycle (2007)

Mammalian cells rely on cellular uptake of the essential amino acid tryptophan. Tryptophan sequestration by up-regulation of the key enzyme for tryptophan degradation, indoleamine 2,3-dioxygenase (IDO), e.g., in cancer and inflammation, is thought to suppress the immune response via T cell starvation. Additionally, the excreted tryptophan catabolites (kynurenines) induce apoptosis of lymphocytes. Whereas tryptophan transport systems have been identified, the molecular nature of kynurenine export remains unknown. To measure cytosolic tryptophan steady-state levels and flux in real time, we developed genetically encoded fluorescence resonance energy transfer nanosensors (FLIPW). The transport properties detected by FLIPW in KB cells, a human oral cancer cell line, and COS-7 cells implicate LAT1, a transporter that is present in proliferative tissues like cancer, in tryptophan uptake. Importantly, we found that this transport system mediates tryptophan/kynurenine exchange. The tryptophan influx/kynurenine efflux cycle couples tryptophan starvation to elevation of kynurenine serum levels, providing a two-pronged induction of apoptosis in neighboring cells. The strict coupling protects cells that overproduce IDO from kynurenine accumulation. Consequently, this mechanism may contribute to immunosuppression involved in autoimmunity and tumor immune escape.
Mechanisms of Human Atrial Fibrillation Initiation (2012)

Steep APD restitution is a common pathway for AF initiation by isoproterenol and tachycardia via reduced activation latency that enables engagement of steep APD restitution at rapid rates. Modeling suggests that AF initiation from each intervention uses distinct ionic mechanisms. This insight may help design interventions to prevent AF.
Novel WDM passive optical network with bidirectional protection (2002)

Passive optical networks (PONs) have recently emerged to be a promising approach to enhance the penetration of fiber towards the subscriber side, thus further enables delivery of higher data-rate services to the subscribers. They feature easy network maintenance as there is no active component at the remote node (RN). However, in conventional PONs, both upstream and downstream bandwidths have to be time-shared among all optical network units (ONUs). By applying WDM technique to PONs, the total system capacity can be further enhanced. Each ONU enjoys a dedicated bandwidth and resolves the ranging problem as in PONs. In both conventional PON and WDM-PON, little work has been done to offer protection capability though fiber fault detection methods have been extensively studied. We propose a novel network architecture for WDM-PON which offers 1:1 protection capability. In case of any fiber cut between remote node and ONUs, the affected ONU can re-route the wavelength channels via the adjacent ONU and can still maintain normal bidirectional traffic.
The Nitrosation of Hexetidine and Hexedine: Characterization of the Major Nitrosamine from Common Antimicrobial Agents (1994)

The acidic nitrosation of hexetidine and hexedine, common antimicrobial agents and drug constituents, leads to a mixture of nitrosamines. The major nitrosamine product, "HEXNO", forms rapidly in yields as high as 60% over the pH range 1-4.8 at incubation times of 1 h at 37 degrees C with 40 mM NO2- and 10 mM hexetidine. On the basis of extensive spectroscopic characterization and independent synthesis HEXNO has been assigned the structure of 1-(2-ethylhexyl)-3-nitroso-4-methyl-4-[[N-(2-ethylhexyl)-N- nitrosoamino]methyl]imidazolidine (7). The synthesis of HEXNO involves the novel interception by potassium nitrite in ether/18-crown-6 of an imminium ion produced from the reaction of hexedine with benzyl chloroformate. Collapse of the alpha-amino nitrous ester produced by this reaction yields the nitrosamine containing carbamate 8, which yields HEXNO after removal of the carbamate with trimethylsilyl iodide and subsequent nitrosation. The rapid formation of HEXNO from hexetidine and hexedine supports the hypothesis that tertiary geminal diamines will produce nitrosamines rapidly by a mechanism which involves the cleavage of a nitrosammonium ion with the assistance of the neighboring nitrogen atom. This process is deemed to be of possible importance in the endogenous production of potentially carcinogenic nitrosamines because of its low nitrite requirement and high nitrosation rate. The available data suggest the probable formation of HEXNO and other nitrosamines from hexetidine under conditions of its use.
GaAs epitaxy on Si substrates: modern status of research and engineering (2008)

While silicon and gallium arsenide are dominant materials in modern micro- and nanoelectronics, devices fabricated from them still use Si and GaAs substrates only separately. Integrating these materials on the (highest effeciency) substrate of Si has been the subject of much research effort for more than twenty years. This review systematizes and generalizes the current understanding of the fundamental physical mechanisms governing the epitaxial growth of GaAs and its related III–V compounds on Si substrates. Basic techniques avilable for improving the quality of such heterostructures are described, and recent advances in fabricating device-quality AIIIBV/Si heterostructures and devices on their bases are also presented.
Inhibition of glucocorticoid‐induced epidermal and dermal atrophy with KH 1060 – a potent 20‐epi analogue of 1,25‐dihydroxyvitamin D3 (1994)

1. The possibility of preventing and treating glucocorticoid-induced skin atrophy with KH 1060 (the potent 20-epi-22-oxa-24a-homo-26,27-dimethyl analogue of 1,25-dihydroxyvitamin D3) was examined in a hairless mouse model. 2. KH 1060 (0.625-6.25 pmol cm-2 of skin) applied topically for 7 days together with 2.5 nmol cm-2 betamethasone-17-valerate prevented, in a concentration-dependent manner, the development of epidermal, dermal and total skin thinning caused by the glucocorticoid. The effect of KH 1060 on the epidermis occurred at a lower dose than on the dermis, and at doses above 1.25 pmol cm-2 KH 1060 caused epidermal hyperplasia. 3. KH 1060 (2.5 pmol cm-2) prevented the development of betamethasone-associated skin atrophy in mice during a long-term (4 weeks) treatment, and reversed established cutaneous glucocorticoid atrophy. 4. Radiolabelling experiments with [35S]-sulphate and [3H]-proline in vivo revealed that KH 1060 stimulated the synthesis of sulphated glycosaminoglycans and hydroxyproline in skin treated with betamethasone. 5. These findings strongly suggest that KH 1060 prevents and reverses glucocorticoid-induced skin atrophy by stimulating epidermal proliferation and enhancing synthesis of extracellular matrix in the dermis.
A eukaryotic cytosolic chaperonin is associated with a high molecular weight intermediate in the assembly of hepatitis B virus capsid, a multimeric particle. (1994)

We have established a system for assembly of hepatitis B virus capsid, a homomultimer of the viral core polypeptide, using cell-free transcription-linked translation. The mature particles that are produced are indistinguishable from authentic viral capsids by four criteria: velocity sedimentation, buoyant density, protease resistance, and electron microscopic appearance. Production of unassembled core polypeptides can be uncoupled from production of capsid particles by decreasing core mRNA concentration. Addition of excess unlabeled core polypeptides allows the chase of the unassembled polypeptides into mature capsids. Using this cell-free system, we demonstrate that assembly of capsids proceeds by way of a novel high molecular weight intermediate. Upon isolation, the high molecular weight intermediate is productive of mature capsids when energy substrates are manipulated. A 60-kD protein related to the chaperonin t-complex polypeptide 1 (TCP-1) is found in association with core polypeptides in two different assembly intermediates, but is not associated with either the initial unassembled polypeptides or with the final mature capsid product. These findings implicate TCP-1 or a related chaperonin in viral assembly and raise the possibility that eukaryotic cytosolic chaperonins may play a distinctive role in multimer assembly apart from their involvement in assisting monomer folding.
Mechanical factors determining maximum bronchoconstriction. (1989)

The principal feature which distinguishes asthmatics from normal subjects is that their airways constrict excessively to stimuli, to the extent that airway narrowing exceeds the maximum degree of bronchoconstriction which occurs in normal subjects. The load against which bronchial smooth muscle contracts is a very important determinant of the degree of airway narrowing. The elastic properties of the airway wall itself and the interdependence between the airways and the surrounding parenchyma are the elastic load which bronchial smooth muscle has to overcome to narrow the airway. The most likely explanation of a decreased load in asthma is oedema of the airway wall, because it may unlink the interdependence between the airway and the surrounding parenchyma.
Influence of Catheter Orientation, Tissue Thickness and Conduction Velocity on the Intracardiac Electrogram (2013)

Intracardiac electrograms are essential for the diagnosis and treatment of various cardiac arrhythmias. To gain reliable information about structural alterations of underlying tissue, it is necessary to interpret these electrograms correctly. Therefore it has to be understood how other parameters influence the signal. Realistic 3D geometries were created and simulated using the bidomain model. Based on these simulations, the influences of catheter orientation, tissue thickness and conduction velocity on the amplitudes of intracardiac electrograms were evaluated.
Cell-based field effect devices for cell adhesion analysis (2006)

We have developed cell-based field effect devices for cell adhesion analysis. Mouse fibroblast cells were adhered on the Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3 </sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> gate surface of the field effect devices. Attachment and detachment of the cell could be detected as a shift of the flat hand voltage of the field effect devices based on the negative charges of sialic acid at the surface of the cell membrane. Quantitative analysis of cell adhesion could be demonstrated when diluted cell samples are used. The cell-based field effect devices are useful to study cell adhesion characteristics on different surface materials and structures as well as cell functional analysis
Gabapentin (neurontin) and S‐(+)‐3‐isobutylgaba represent a novel class of selective antihyperalgesic agents (1997)

1. Gabapentin (neurontin) is a novel antiepileptic agent that binds to the alpha 2 delta subunit of voltage-dependent calcium channels. The only other compound known to possess affinity for this recognition site is the (S)-(+)-enantiomer of 3-isobutylgaba. However, the corresponding (R)-(-)-enantiomer is 10 fold weaker. The present study evaluates the activity of gabapentin and the two enantiomers of 3-isobutylgaba in formalin and carrageenan-induced inflammatory pain models. 2. In the rat formalin test, S-(+)-3-isobutylgaba (1-100 mg kg-1) and gabapentin (10-300 mg kg-1) dose-dependently inhibited the late phase of the nociceptive response with respective minimum effective doses (MED) of 10 and 30 mg kg-1, s.c. This antihyperalgesic action of gabapentin was insensitive to naloxone (0.1-10.0 mg kg-1, s.c.). In contrast, the R-(-)-enantiomer of 3-isobutylgaba (1-100 mg kg-1) produced a modest inhibition of the late phase at the highest dose of 100 mg kg-1. However, none of the compounds showed any effect during the early phase of the response. 3. The s.c. administration of either S-(+)-3-isobutylgaba (1-30 mg kg-1) or gabapentin (10-100 mg kg-1), after the development of peak carrageenan-induced thermal hyperalgesia, dose-dependently antagonized the maintenance of this response with MED of 3 and 30 mg kg-1, respectively. Similar administration of the two compounds also blocked maintenance of carrageenan-induced mechanical hyperalgesia with MED of 3 and 10 mg kg-1, respectively. In contrast, R-(-)-3-isobutylgaba failed to show any effect in the two hyperalgesia models. 4. The intrathecal administration of gabapentin dose-dependently (1-100 micrograms/animal) blocked carrageenan-induced mechanical hyperalgesia. In contrast, administration of similar doses of gabapentin into the inflamed paw was ineffective at blocking this response. 5. Unlike morphine, the repeated administration of gabapentin (100 mg kg-1 at start and culminating to 400 mg kg-1) over 6 days did not lead to the induction of tolerance to its antihyperalgesic action in the formalin test. Furthermore, the morphine tolerance did not cross generalize to gabapentin. The s.c. administration of gabapentin (10-300 mg kg-1), R-(-) (3-100 mg kg-1) or S-(+)-3-isobutylgaba (3-100 mg kg-1) failed to inhibit gastrointestinal motility, as measured by the charcoal meal test in the rat. Moreover, the three compounds (1-100 mg kg-1, s.c.) did not generalize to the morphine discriminative stimulus. Gabapentin (30-300 mg kg-1) and S-(+)-isobutylgaba (1-100 mg kg-1) showed sedative/ataxic properties only at the highest dose tested in the rota-rod apparatus. 6. Gabapentin (30-300 mg kg-1, s.c.) failed to show an antinociceptive action in transient pain models. It is concluded that gabapentin represents a novel class of antihyperalgesic agents.