gebhart/patrepeval huggingface dataset:
Cytokine-dependent gp130 receptor subunit regulates human fetal pituitary adrenocorticotropin hormone and growth hormone secretion. (1997)

We have shown recently that leukemia inhibitory factor (LIF) and oncostatin M (OSM), two members of the gp130-dependent cytokine family, stimulate murine proopiomelanocortin (POMC) transcription and adrenocorticotropin hormone (ACTH) secretion. LIF and corticotropin-releasing hormone (CRH) also synergistically induced in vivo ACTH secretion in fetal nonhuman primates. To elucidate the role of the gp130-related cytokines in human pituitary hormone regulation, we tested expression of gp130-related cytokine receptors in human fetal pituitaries. Using RT-PCR, mRNA expression of receptors for LIF, IL-6, and CRH, and the gp130 subunit, were all detected in fetal pituitaries of 18- and 31-wk gestation. Recombinant human IL-6, LIF, and OSM treatments of primary human fetal pituitary cultures (16-31 wk) increased ACTH secretion by up to 48% (P < 0.05) using doses of 1 nM, and when fetal cultures were cotreated with CRH, ACTH was induced five- to sixfold as compared to CRH alone (three- to fourfold; P = 0.01). Incubation with gp130-specific antibody suppressed basal and cytokine-stimulated ACTH secretion (alone or with CRH) from human fetal cells. Human POMC promoter -879/+6 fused to the luciferase reporter gene and transfected into AtT-20 cells, was stimulated by LIF (7-fold), which also exerted strong (22-fold) synergy with CRH on POMC transcription. Growth hormone (GH) release from fetal cultures was modestly stimulated (15-31%, P < 0.05), while other anterior pituitary hormones were not altered by these cytokines. Thus, physiologic concentrations of the gp130-related cytokines have direct effects on ACTH and GH regulation in the human pituitary, indicating that gp130-dependent signals serve as a paracrine system controlling early human pituitary function.
Relationship between the anticoagulant and antithrombotic effects of heparin in experimental venous thrombosis (1977)

The relationship between the antithrombotic and anticoagulant effects of heparin was assessed using venous thrombi in rabbits. Accretion of 125I-fibrinogen onto jugular vein thrombi was used to assess the antithrombotic effect of heparin, and the protamine sulfate titration test (heparin activity) and the activated partial thromboplastin time (APTT) were used to measure its anticoagulant effect. The effect of heparin on jugular vein bleeding times was also measured in a separate group of animals. Fibrinogen accretion was significantly lower with continuous infusion than with intermittent injection. Heparin, given by continuous infusion, produced marked inhibition of fibrinogen accretion (to less than 10% of control accretion) at an APTT value of between 75 and 80 sec (control 34 sec) and at a level of heparin activity of 0.4-0.5 U/ml. Infusion of cryoprecipitate reduced the effect of heparin on the APTT relative to its effect on heparin activity. In these cryoprecipitate-treated animals, marked inhibition of fibrinogen accretion occurred at a similar level of heparin activity (0.4-0.6 U/ml) but at a significantly lower APTT (35-50 sec) than in normal animals. On the other hand, there was a progressive increase in jugular vein bleeding time with both increasing APTT values and heparin levels in both groups of animals.
Detection of Disseminated Urothelial Cancer Cells in Peripheral Venous Blood by a Cytokeratin 20‐specific Nested Reverse Transcriptase‐Polymerase Chain Reaction (1999)

More than half of all patients with invasive urothelial cancer subsequently develop metastatic disease even after radical resection of the primary cancer. In these patients, neoplastic cells may be disseminated prior to or during the operation. A nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) assay which amplifies cytokeratin (CK) 20 transcripts was used to detect cancer cells in the peripheral blood of urothelial patients. This assay was able to detect 10 bladder cancer cell line cells in a sample of ten million peripheral-blood mononuclear (PBMN) cells. CK 20-specific signals were detected in 9 (22.5%) of 40 PBMN cell samples prepared from 40 urothelial cancer patients in relation to the tumor stage, including 0/13 patients with a superficial tumor, 4/21 (19%) with a regionally invasive tumor and 5/6 (83%) with a metastatic tumor (P = 0.0002 in chi 2 test). No signals were detected in any of 25 healthy donor PBMN cell samples. The present results indicate that the CK 20 RT-PCR assay is applicable for detection of urothelial cancer cells in the peripheral blood. The assay also confirms that hematogenic dissemination occurs in invasive urothelial cancers but rarely in superficial ones.
Expression of p53 in human neuroblastoma- and neuroepithelioma-derived cell lines. (1992)

Overexpression of the nuclear phosphoprotein p53 has been detected in many different transformed human cell lines and primary adult tumors. Elevated steady-state levels of p53 appear to be the result of an increase in the stability of the protein and, in adult cancers, high levels of the protein are associated with mutation of the p53 gene. In this study, overexpression of p53 was detected in 4 out of 5 human neuroblastoma-derived cell lines. The protein expressed by each of these four lines had a significantly prolonged half-life relative to the p53 protein in immortalized rodent fibroblasts and normal bovine adrenal medullary cells. However, no mutations were detected in the highly conserved regions of the p53 gene in these four neuroblastoma lines and the protein being expressed was not recognized by the mutant-specific anti-p53 monoclonal antibody, PAb 240. Upon retinoic acid-induced differentiation of the LA-N-5 neuroblastoma cell line, the level of p53 protein declined, as did the level of p53 mRNA, but the half-life of the protein remained unchanged. The high level of protein observed in the undifferentiated cell lines appears to result from expression of a stable wild-type p53 protein and increased transcription. In contrast, p53 protein was undetectable in two neuroepithelioma-derived cell lines; the p53 gene in one of these lines contained a nonsense mutation, while the other transcribed truncated p53 mRNA.
Solution Structure of the IIB Domain of the Glucose Transporter of Escherichia coli (1996)

The structure of the IIBGlc domain of the Escherichia coli transporter for glucose was determined by multidimensional heteronuclear NMR. The glucose transporter (IICBGlc) belongs to the bacterial phosphotransferase system. It mediates uptake with concomittant phosphorylation of glucose. The N-terminal IICGlc domain spans the membrane, the C-terminal IIBGlc domain (residues 386-477) contains the phosphorylation site, Cys421. The structure of the subclonal IIB domain was determined based on 927 conformational constraints, including 744 NOE derived upper bounds, 43 constraints of ranges of dihedral angles based on measurements of vicinal coupling constants, and 70 upper and lower bound constraints associated with 35 hydrogen bonds. The distance geometry interpretation of the NMR data is based on the previously published sequence-specific 1H, 15N, and 13C resonance assignments [Golic Grdadolnik et al. (1994) Eur. J. Biochem. 219, 945-952]. The sequence of the secondary structure elements of IIB is alpha 1 beta 1 beta 2 alpha 2 beta 3 beta 4 alpha 3. The basic fold consists of a split alpha/beta-sandwich composed of an antiparallel sheet with strand order beta 1 beta 2 beta 4 beta 3 and three alpha-helices superimposed onto one side of the sheet. The hydrophobic helix alpha 1 is packed against helices alpha 2, alpha 3, and the beta-sheet. The phosphorylation site (Cys421) is at the end of beta 1 on the solvent-exposed face of the sheet surrounded by Asp419, Thr423 Arg424, Arg426, and Gln456 which are invariant in 15 homologous IIB domains from other PTS transporters.
Role of interleukin 6 in fever in rats (1990)

The purpose of these studies was to assess whether interleukin 6 (IL-6) is an endogenous pyrogen, responsible for all or part of the fever caused by lipopolysaccharide (LPS) in rats. We have found that the core temperature (as measured by biotelemetry) rose significantly after intracerebroventricular (icv) injection of recombinant human IL-6. The same doses of IL-6, when administered intravenously or intraperitoneally, had no effect on body temperature. The fever caused by icv administration of IL-6 was completely blocked by indomethacin. After injection of fever-inducing doses of LPS, the plasma and cerebrospinal fluid (CSF) IL-6 activities rose, the former much more than the latter. The correlation between fever and plasma IL-6 activity was r = 0.84 (P less than 0.0025); the correlation between fever and CSF IL-6 activity was r = 0.77 (P less than 0.015). The results of this study are consistent with the hypothesis that IL-6 is a mediator of LPS-induced fever in the rat.
Mammalian collagen IV (2008)

Four decades have passed since the first discovery of collagen IV by Kefalides in 1966. Since then collagen IV has been investigated extensively by a large number of research laboratories around the world. Advances in molecular genetics have resulted in identification of six evolutionary related mammalian genes encoding six different polypeptide chains of collagen IV. The genes are differentially expressed during the embryonic development, providing different tissues with specific collagen IV networks each having unique biochemical properties. Newly translated alpha-chains interact and assemble in the endoplasmic reticulum in a chain-specific fashion and form unique heterotrimers. Unlike most collagens, type IV collagen is an exclusive member of the basement membranes and through a complex inter- and intramolecular interactions form supramolecular networks that influence cell adhesion, migration, and differentiation. Collagen IV is directly involved in a number of genetic and acquired disease such as Alport's and Goodpasture's syndromes. Recent discoveries have also highlighted a new and direct role for collagen IV in the development of rare genetic diseases such as cerebral hemorrhage and porencephaly in infants and hemorrhagic stroke in adults. Years of intensive investigations have resulted in a vast body of information about the structure, function, and biology of collagen IV. In this review article, we will summarize essential findings on the structural and functional relationships of different collagen IV chains and their roles in health and disease.
Subtle Neuromuscular Defects in Utrophin-deficient Mice (1997)

Utrophin is a large cytoskeletal protein that is homologous to dystrophin, the protein mutated in Duchenne and Becker muscular dystrophy. In skeletal muscle, dystrophin is broadly distributed along the sarcolemma whereas utrophin is concentrated at the neuromuscular junction. This differential localization, along with studies on cultured cells, led to the suggestion that utrophin is required for synaptic differentiation. In addition, utrophin is present in numerous nonmuscle cells, suggesting that it may have a more generalized role in the maintenance of cellular integrity. To test these hypotheses we generated and characterized utrophin-deficient mutant mice. These mutant mice were normal in appearance and behavior and showed no obvious defects in muscle or nonmuscle tissue. Detailed analysis, however, revealed that the density of acetylcholine receptors and the number of junctional folds were reduced at the neuromuscular junctions in utrophin-deficient skeletal muscle. Despite these subtle derangements, the overall structure of the mutant synapse was qualitatively normal, and the specialized characteristics of the dystrophin-associated protein complex were preserved at the mutant neuromuscular junction. These results point to a predominant role for other molecules in the differentiation and maintenance of the postsynaptic membrane.
Aggregation of red blood cells in patients with Gaucher disease (2006)

Gaucher disease is associated with increased red blood cell (RBC) aggregation, but the pathophysiological significance of this phenomenon and its correlation with disease manifestations are unclear. RBC aggregation was evaluated in 43 patients with Gaucher disease and 53 healthy controls. Dynamic RBC aggregation was examined in a narrow-gap flow chamber at varying shear stress. Compared with the controls, RBC aggregation in Gaucher disease was increased by 25%. Comparison of RBC aggregation in autologous plasma and in dextran (500 kDa) showed an increase both in plasma-dependent (extrinsic) and -independent (intrinsic) RBC aggregation. Subgroup analysis revealed that increased RBC aggregation was limited to patients with an intact spleen. RBC aggregation in patients did not correlate with plasma fibrinogen concentration, disease severity, enzyme replacement therapy or genotype. We conclude that RBC aggregation is increased in patients with Gaucher disease and an intact spleen, possibly reflecting the accumulation of glucocerebroside and other substances in the plasma and RBC membranes of these patients. Our results do not support a role for RBC aggregation in the pathogenesis of vascular complications of Gaucher disease.
SOME COMPONENTS OF THE TUMOR‐LOCALIZING FRACTION OF HEMATOPORPHYRIN DERIVATIVE (1990)

In continuation of the effort to delineate the structure of Photofrin, a chromatographically well separated component of the tumor-localizing fraction was isolated and purified using a combination of gel filtration chromatography and semi-preparative high-performance liquid chromatography. This component, the least hydrophobic of the tumor-localizing fraction, was deemed to be dihematoporphyrin ether, based on mass spectrometric analysis and its behavior toward base hydrolysis and lithium aluminum hydride reduction. Although less potent than Photofrin, the purified component was an active photosensitizer.
Main chain and side chain chiral methylated somatostatin analogs: syntheses and conformational analyses (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMain chain and side chain chiral methylated somatostatin analogs: syntheses and conformational analysesZiwei Huang, Ya Bo He, Karen Raynor, Melanie Tallent, Terry Reisine, and Murray GoodmanCite this: J. Am. Chem. Soc. 1992, 114, 24, 9390–9401Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/ja00050a019https://doi.org/10.1021/ja00050a019research-articleACS PublicationsRequest reuse permissionsArticle Views346Altmetric-Citations112LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Contextual word similarity and estimation from sparse data (1993)

In recent years there is much interest in word cooccurrence relations, such as n-grams, verb-object combinations, or cooccurrence within a limited context. This paper discusses how to estimate the probability of cooccurrences that do not occur in the training data. We present a method that makes local analogies between each specific unobserved cooccurrence and other cooccurrences that contain similar words, as determined by an appropriate word similarity metric. Our evaluation suggests that this method performs better than existing smoothing methods, and may provide an alternative to class based models.
Synthesis, Complexation and Pharmaceutical Applications of Tetra‐directional Cascade Dendrimers* (1996)

A synthetic strategy based on repetitive, divergent, stepwise growth has been used to prepare a tetra-directional cascade dendrimer with a modified peripheral layer.



The study of host-guest interactions with this new type of container molecule indicated that complexation increased the solubility of different hydrophobic guests (benzoic acid, 1-naphthoic acid and 9-anthracenecarboxylic acid) which are sparingly soluble in water. Flow microcalorimetric analysis confirmed the effectiveness of suitable drug-dendrimer complexes.



The size of the cavity within the dendrimer plays a vital role in the accommodation of the guest.
Performance Evaluation of a Hybrid Linear Ion Trap/Orbitrap Mass Spectrometer (2006)

Design and performance of a novel hybrid mass spectrometer is described. It couples a linear ion trap mass spectrometer to an orbitrap mass analyzer via an rf-only trapping quadrupole with a curved axis. The latter injects pulsed ion beams into a rapidly changing electric field in the orbitrap wherein they are trapped at high kinetic energies around an inner electrode. Image current detection is subsequently performed after a stable electrostatic field is achieved. Fourier transformation of the acquired transient allows wide mass range detection with high resolving power, mass accuracy, and dynamic range. The entire instrument operates in LC/MS mode (1 spectrum/s) with nominal mass resolving power of 60,000 and uses automatic gain control to provide high-accuracy mass measurements, within 2 ppm using internal standards and within 5 ppm with external calibration. The maximum resolving power exceeds 100,000 (fwhm). Rapid, automated data-dependent capabilities enable real-time acquisition of up to three high-mass accuracy MS/MS spectra per second.
In Situ Expression of the Cell Adhesion Molecules in Bronchial Tissues from Asthmatics with Air Flow Limitation: In Vivo Evidence of VCAM-1/VLA-4 Interaction in Selective Eosinophil Infiltration (1995)

Eosinophils play a critical role in the pathogenesis of bronchial asthma by releasing various mediators. To understand the mechanisms of eosinophil migration to the site of inflammation, we examined the expression of adhesion molecules in the bronchial tissues of asthmatic subjects with air flow limitation. By immunohistochemical analysis, Mac-1, LFA-1, and VLA-4 were strongly positive in eosinophils and mononuclear cells infiltrated in the bronchial mucosa and submucosa. Their number was significantly increased compared with those in control tissue. Immunolocalization for ICAM-1, the ligand of Mac-1 and LFA-1, was detected in the endothelial cells of capillaries and venules, in the mononuclear cells in submucosa, and in the basal layer of the epithelium. Endothelial cells in capillaries and venules were also strongly positive for VCAM-1, the ligand of VLA-4. Immunolocalization for E-selectin was detected in some endothelial cells in capillaries and venules in bronchial submucosa, whereas there were very few positive cells in the bronchial tissues from control subjects. In situ hybridization demonstrated ICAM-1 mRNA expression in the endothelial cells and mononuclear cells in bronchial submucosa. Immunoelectron microscopy for ICAM-1, VCAM-1, and E-selectin demonstrated de novo synthesis of these molecules and their expression along the luminal cell membrane of endothelial cells. These results suggested that ICAM-1, VCAM-1, and E-selectin were newly synthesized prior to spontaneous asthma attacks, and that their expression, particularly that of VCAM-1, may play a key role in eosinophil infiltration into the airway.
Three-dimensional optical interconnects by stacked ARROW waveguides (1993)

To establish three-dimensional dense interconnects in integrated photonic circuits, a new stacked configuration of ARROW waveguides is developed. The crosstalk-free propagation and power exchange in the stacked ARROW-B wave-guides are experimentally demonstrated.
Impact of Bosentan on Exercise Capacity in Adults After the Fontan Procedure: A Randomized Controlled Trial (2013)

An increased NT-proBNP level was present in the majority of Fontan patients. Six months of bosentan treatment was not beneficial. Trial registration NTR1557.
Utility of Aspergillus Antigen Detection in Specimens Other than Serum Specimens (2004)

The detection of circulating galactomannan in serum is an important tool for the early diagnosis of invasive aspergillosis. A commercial enzyme-linked immunosorbent assay (Platelia Aspergillus; BioRad) was shown to be both highly sensitive and specific for detection of galactomannan in serum samples. Despite the fact that this assay is validated for serum samples, specimens of other body fluids are increasingly used for detection of galactomannan, including urine, bronchoalveolar lavage fluid, and cerebrospinal fluid. Review of the literature shows that galactomannan can be detected in each of these samples from patients with invasive aspergillosis with higher sensitivity than is the case with culture, as well as early in the course of infection. However, the evidence thus far is based on case reports--predominantly retrospective studies--that often include heterogeneous patient populations and limited numbers of cases of proven infection. Clearly, well-designed prospective studies with systematic sampling and use of consensus case definitions are needed to compare the performance of antigen detection in samples other than serum specimens with that in serum specimens.
Essential Role of Phosphoinositide 3-Kinase δ in Neutrophil Directional Movement (2003)

Neutrophil chemotaxis is a critical component of the innate immune response. Neutrophils can sense an extremely shallow gradient of chemoattractants and produce relatively robust chemotactic behavior. This directional migration requires cell polarization with actin polymerization occurring predominantly in the leading edge. Synthesis of phosphatidylinositol (3,4,5) trisphosphate (PIP3) by phosphoinositide 3-kinase (PI3K) contributes to asymmetric F-actin synthesis and cell polarization during neutrophil chemotaxis. To determine the contribution of the hemopoietic cell-restricted PI3K delta in neutrophil chemotaxis, we have developed a potent and selective PI3K delta inhibitor, IC87114. IC87114 inhibited polarized morphology of neutrophils, fMLP-stimulated PIP3 production and chemotaxis. Tracking analysis of IC87114-treated neutrophils indicated that PI3K delta activity was required for the directional component of chemotaxis, but not for random movement. Inhibition of PI3K delta, however, did not block F-actin synthesis or neutrophil adhesion. These results demonstrate that PI3K delta can play a selective role in the amplification of PIP3 levels that lead to neutrophil polarization and directional migration.