gebhart/patrepeval huggingface dataset:
Structural characterization of heparan sulfate proteoglycan subclasses isolated from bovine aortic endothelial cell cultures (1988)

Labeled heparan sulfate proteoglycans (HSPG) were isolated from wounded and confluent cultures of bovine aortic endothelial cells by nondegradative extraction with 4 M guanidine hydrochloride and detergent. HSPG were separated from more highly charged chondroitin or dermatan sulfate proteoglycans by ion-exchange chromatography, and subclasses of different hydrodynamic size were isolated by gel filtration. Three major subclasses of HSPG were characterized structurally with respect to the presence and relative size of protein core, the presence and amount of nonsulfated oligosaccharide, and size and structure of heparan sulfate (HS) chains. The largest (600-800-kDa) HSPG subclass (I), isolated from cell layers and media of confluent cultures, bears 38-kDa HS chains on an apparently heterogeneous class of relatively large glycoprotein cores. HSPG II (150-200 kDa), isolated from cell layer or media, has 22-kDa HS chains and smaller core glycoproteins (less than 50 kDa). HSPG III, the subclass of smallest hydrodynamic size, has 13-kDa HS chains and a glycopeptide core of less than 15 kDa. All subclasses bear varying proportions of non-sulfated oligosaccharides of similar sizes. Comparisons of HS chain structure indicated that the different subclasses have similar proportions (49-55%) of N-sulfate, with both O-sulfate and highly N-sulfated blocks of disaccharide distributed similarly along HS chains. In addition, HS chains from subclasses II and III contain sequences that are insensitive to periodate oxidation or heparitinase digestion, suggesting that they contain increased proportions of iduronate.(ABSTRACT TRUNCATED AT 250 WORDS)
The endogenous Bacillus subtilis (natto) plasmids pTA1015 and pTA1040 contain signal peptidase‐encoding genes: identification of a new structural module on cryptic plasmids (1995)

Various strains of Bacillus subtilis (natto) contain small cryptic plasmids that replicate via the rolling-circle mechanism. Like plasmids from other Gram-positive bacteria, these plasmids are composed of several distinct structural modules. A new structural module was identified on the B. subtilis plasmids pTA1015 and pTA1040. It is composed of two genes: one specifies an unidentified protein with a putative signal peptide; and the other (sipP) specifies a functional type 1 signal peptidase (SPase). The homologous, but non-identical, sipP genes of the two plasmids are the first identified plasmid-specific SPase-encoding genes. With respect to structure and activity, the corresponding enzymes (denoted SipP) are highly similar to the chromosomally encoded SPase, SipP, of B. subtillis and several newly identified SPases of other bacilli. Our findings suggest that plasmid-encoded SPases have evolved because, of under certain conditions, SPase can be a limiting factor for protein secretion in B. subtilis.
RECENT IMPROVEMENTS TOWARDS THE SYNTHESIS OF THE C-GLUCURONOSYL CANCER CHEMOPREVENTIVE (β-d-GLUCOPYRANOSYLURONATE)-4-RETINAMIDOPHENYLMETHANE (1996)

Evidence suggests that the glucuronide conjugates of retinoids may be active metabolites of the parent compounds with potential utility as drugs.1 We have recently shown that the O-glucuronide metabolite 1 of the synthetic retinoid N-4-hydroxyphenylretinamide (2) shows reduced toxicity and a significant chemopreventive advantage relative to the parent retinoid in a carcinogen-induced rat mammary cancer model.2 In efforts to determine whether these conjugates function as intact molecules or must be hydrolyzed back to 2, we designed and synthesized a series of C-glycosyl and C-glucuronosyl analogues of 1 3. Our syntheses of these compounds are lengthy (10-12 steps) and lead to the desired products in less than 4% overall yields. Limitations on the availability of these compounds led us to evaluate them using a modified protocol for the carcinogen-induced rat mammary tumor model. While many of our analogues showed cancer chemopreventive activity in this assay, C-glucuronosyl analogue 3 has proven to be the most effective analogue of 2 we have yet evaluated in this model.4 Unfortunately, compound 3 was prepared in the poorest overall yield among these analogues. However, its potent activity and low toxicity make it an important candidate for expanded biological studies. Because additional studies of this important new compound will benefit from improvements in its synthesis, we briefly describe below recent dramatic improvements we have made in the preparation of 3.
Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes (1993)

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a polypeptide mediator, elaborated by certain tumors and other cell types, that exerts multiple effects on endothelium via interaction with a class of high-affinity binding sites. In this report, the interaction of VPF/VEGF with human mononuclear phagocytes (MPs) is characterized. Radioligand binding studies at 4 degrees C showed the presence of a single class of binding sites, kd approximately 300 to 500 pmol/L (approximately 20 times lower affinity than the high-affinity binding site on endothelial cells [ECs]), the occupancy of which correlated with VPF/VEGF-induced MP migration and expression of tissue factor. These binding results were paralleled by functional experiments which indicated that the same VPF/VEGF preparations were about an order of magnitude less effective in stimulating MP chemotaxis than in inducing EC proliferation. When MPs with surface-bound 125I-VPF/VEGF were warmed to 37 degrees C, endocytosis and degradation occurred. Occupancy of VPF/VEGF binding site resulted in subsequent activation of intracellular signal transduction mechanisms, as shown by an increase in MP intracellular calcium concentration. Cross-linking studies with 125I-VPF/VEGF showed a new high-molecular weight band (corresponding to putative 125I- VPF/VEGF-receptor complex), the appearance of which was blocked by excess unlabeled VPF/VEGF. Consistent with these results, immunoprecipitation of 32PO4-labeled MPs exposed to VPF/VEGF showed a single band of similar mobility, not seen in untreated controls. These results demonstrate that the interaction of VPF/VEGF with MPs, though of lower affinity than that observed with ECs, also results from interaction of the polypeptide with a specific cell-surface protein and leads to activation of intracellular transduction mechanisms.
Finding Partners: Emerging Protein Interaction Technologies Applied to Signaling Networks (2003)

Signal transduction pathways play essential roles in cell differentiation, proliferation, and survival. Their precise regulation is achieved through specific protein-protein interactions that mediate the assembly of protein complexes in response to different signals. Disturbances of the normal protein-protein interactions within signaling pathways can lead to many diseases, including cancer. In this review, Stagljar aims to highlight the emerging protein interaction technologies that are advancing the field of signal transduction. These approaches include stable isotope labeling by amino acids in cell culture, SH2 profiling, target-assisted iterative screening, and the split-ubiquitin membrane yeast two-hybrid system. Although still at an early stage, these technologies show promise as useful methods for the characterization of novel components of various signal transduction pathways.
Advances in the management of endometriosis: an update for clinicians (2005)

Endometriosis is a chronic and recurrent disease characterized by the presence and proliferation of endometrial tissue outside the uterine cavity, which occurs in approximately 10% of women of reproductive age. In this estrogen-dependent disorder, lesions become inactive and gradually undergo regression during states of ovarian down-regulation, such as amenorrhoea or menopause. The impact of endometriosis includes impaired fertility potential, as well as symptoms of dysmenorrhoea, dyspareunia and chronic non-menstrual pain, all of which adversely affect quality of life. Management of endometriosis focuses on pain relief and includes medical and surgical treatment. Pharmacologic therapies currently in use include combination oral contraceptives (COCs), danazol, GnRH analogues and progestins. Although some agents show efficacy in relieving pain, all differ in their side effects, making it difficult to achieve a balance between efficacy and safety. Efficacy has been demonstrated with danazol or GnRH analogues; however, treatment is limited to 6 months because of significant metabolic side effects. Alternatives for longer-term management of symptoms include add-back therapy with GnRH analogues, COCs or progestins. Newer options for treatment of endometriosis include depot medroxyprogesterone acetate subcutaneous injection, as well as several agents under investigation that may prove to have therapeutic potential.
Global Versus Local Methods in Nonlinear Dimensionality Reduction (2002)

Recently proposed algorithms for nonlinear dimensionality reduction fall broadly into two categories which have different advantages and disadvantages: global (Isomap [1]), and local (Locally Linear Embedding [2], Laplacian Eigenmaps [3]). We present two variants of Isomap which combine the advantages of the global approach with what have previously been exclusive advantages of local methods: computational sparsity and the ability to invert conformal maps.
Characterisation of tropospheric turbulent layersfrom radiosonde data (1998)

Thin cloudy turbulent layers, responsible for tropospheric scintillation on earth-space paths, are proved to be efficiently detected and characterised from radiosonde ascents. Based on one complete year of radiosonde data, statistical distributions of turbulent layer height, thickness and intensity are analysed, as is their seasonal variability.
Role of epigenetic DNA alterations in the pathogenesis of systemic lupus erythematosus. (2004)

Epigenetic alternations in genomic DNA encompass cytosine methylation in cytosine and guanine (CpG) dinucleotide islands, which are usually extended in the promoter and first exon of genes. The DNA methylation is carried out by DNA methyltransferases (DNMT) and it serves as an epigenetic method of gene expression modulation. The epigenetic alternations in genomic DNA have been implicated in the development of malignant and autoimmune diseases. The epigenetic aberration in regulatory DNA sequences may also be responsible for the emergence of changes in the immune system in patients with systemic lupus erythematosus (SLE). The agents 5-azacytidine (azacitidine) and 5-aza-2'-deoxycytidine (decitabine) belong to inhibitors of methyltransferase. These compounds affect the methylation level of promoter sequences and cause phenotypic changes in peripheral blood mononuclear cells (PBMC), which are similar to those observed in PBMC of SLE patients. The lack of methylcytosine in CpG dinucleotides may be responsible for the antigenic properties of microbial DNA. The presence of low-apoptotic methylated DNA fragments has been identified in plasma of SLE patients. These DNA fragments exhibit antigenic properties and may elicit the humoral response responsible for the flare of SLE. The low methylation of CpG residues in the regulatory sequences may also contribute to the elevated expression of human endogenous retroviruses (HERVs) in PBMC of SLE patients. The HERV components exhibit a profound similarity with nuclear antigens and may be responsible for the enhancement of the production of anti-antinuclear antibodies (ANA). Recent advances in the investigation of epigenetic DNA changes have formed the basis of improved understanding of etiopathogenesis of SLE, which may thereby facilitate improvement in therapeutic principles of this disease.
The cancer growth suppressor gene mda- 7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice (1998)

A differentiation induction subtraction hybridization strategy is being used to identify and clone genes involved in growth control and terminal differentiation in human cancer cells. This scheme identified melanoma differentiation associated gene-7 (mda-7), whose expression is up-regulated as a consequence of terminal differentiation in human melanoma cells. Forced expression of mda-7 is growth inhibitory toward diverse human tumor cells. The present studies elucidate the mechanism by which mda-7 selectively suppresses the growth of human breast cancer cells and the consequence of ectopic expression of mda-7 on human breast tumor formation in vivo in nude mice. Infection of wild-type, mutant, and null p53 human breast cancer cells with a recombinant type 5 adenovirus expressing mda-7, Ad.mda-7 S, inhibited growth and induced programmed cell death (apoptosis). Induction of apoptosis correlated with an increase in BAX protein, an established inducer of programmed cell death, and an increase in the ratio of BAX to BCL-2, an established inhibitor of apoptosis. Infection of breast carcinoma cells with Ad.mda-7 S before injection into nude mice inhibited tumor development. In contrast, ectopic expression of mda-7 did not significantly alter cell cycle kinetics, growth rate, or survival in normal human mammary epithelial cells. These data suggest that mda-7 induces its selective anticancer properties in human breast carcinoma cells by promoting apoptosis that occurs independent of p53 status. On the basis of its selective anticancer inhibitory activity and its direct antitumor effects, mda-7 may represent a new class of cancer suppressor genes that could prove useful for the targeted therapy of human cancer.
Stroke prophylaxis in atrial fibrillation: who gets it and who does not? (2006)

Risk stratification using known risk factors of stroke seems to affect warfarin treatment only to a minor degree in clinical practice. Undertreatment was particularly common in patients with paroxysmal AF and in patients aged >80 years and calls for improved clinical routines in accordance with international guidelines.
The feasibility and efficacy of His-Purkinje conduction system pacing in patients with permanent atrial fibrillation and chronic heart failure indicated for cardiac resynchronization therapy (2019)

Background: The aim is to study the feasibility and efficacy of His-Purkinje conduction system pacing (HPCSP) in cardiac resynchronization therapy (CRT) candidates of chronic heart failure with permanent atrial fibrillation (AF). Subjects and Methods: Patients with chronic heart failure and permanent AF (n = 16) were enrolled from the Department of Cardiology, Zhongshan Hospital of Fudan University, from September 2017 to April 2019 in this observational case study. The patients with chronic heart failure (left ventricular ejection fraction [LVEF] <40%) and permanent AF with low ventricular rate were indicated for CRT implantation. The study was approved by the Institutional Ethical Committee of Zhongshan Hospital of Fudan University, China. At baseline, 13 cases had narrow QRS duration (<120 ms) and 3 cases had left bundle branch block with QRS duration >120 ms. HPCSP lead connected to the RA port of the generator was implanted together with conventional biventricular pacing (BVP) and was programmed as HPCSP postprocedure. QRS durations were measured and compared during intrinsic, BVP, and HPCSP. Pacing parameters were measured and compared during postimplantation immediately and 6 months postimplantation. Echocardiogram parameters, New York Heart Association (NYHA) class, and 6-min walking distance (6MWD) were collected and compared between baseline and 6 months postimplantation. Results: QRS durations were significantly different during HPCSP compared with BVP (P < 0.0001). Pacing parameters including threshold and R wave amplitude were not significantly different during postimplantation immediately and 6 months postimplantation, whereas impedance was significantly different (P = 0.028). LVEF, left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, mitral regurgitation, tricuspid annular plane systolic excursion, pulmonary artery systolic pressure, and the percentages of moderate-to-severe mitral regurgitation and tricuspid regurgitation were not significantly different between baseline and 6 months postimplantation, whereas NYHA class and 6MWD were significantly different (P < 0.0001). Conclusion: HPCSP was feasible and effective in CRT candidates of chronic heart failure with permanent AF and low ventricular rate. It could significantly reduce QRS duration as compared to BVP. Moreover, although LVEF was not obviously improved, the pacing parameters were stable and NYHA class and 6MWD were improved during HPCSP at 6-month follow-up.
Human Induced Pluripotent Stem Cell Lines Show Stress Defense Mechanisms and Mitochondrial Regulation Similar to Those of Human Embryonic Stem Cells (2010)

The generation of induced pluripotent stem cells (iPSC) has enormous potential for the development of patient-specific regenerative medicine. Human embryonic stem cells (hESC) are able to defend their genomic integrity by maintaining low levels of reactive oxygen species (ROS) through a combination of enhanced removal capacity and limited production of these molecules. Such limited ROS production stems partly from the small number of mitochondria present in hESC; thus, it was important to determine that human iPSC (hiPSC) generation is able to eliminate the extra mitochondria present in the parental fibroblasts (reminiscent of "bottleneck" situation after fertilization) and to show that hiPSC have antioxidant defenses similar to hESC. We were able to generate seven hiPSC lines from adult human dermal fibroblasts and have fully characterized two of those clones. Both hiPSC clones express pluripotency markers and are able to differentiate in vitro into cells belonging to all three germ layers. One of these clones is able to produce fully differentiated teratoma, whereas the other hiPSC clone is unable to silence the viral expression of OCT4 and c-MYC, produce fully differentiated teratoma, and unable to downregulate the expression of some of the pluripotency genes during the differentiation process. In spite of these differences, both clones show ROS stress defense mechanisms and mitochondrial biogenesis similar to hESC. Together our data suggest that, during the reprogramming process, certain cellular mechanisms are in place to ensure that hiPSC are provided with the same defense mechanisms against accumulation of ROS as the hESC.
Phosphoinositide kinases (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphoinositide kinasesChristopher L. Carpenter and Lewis C. CantleyCite this: Biochemistry 1990, 29, 51, 11147–11156Publication Date (Print):December 1, 1990Publication History Published online1 May 2002Published inissue 1 December 1990https://pubs.acs.org/doi/10.1021/bi00503a001https://doi.org/10.1021/bi00503a001research-articleACS PublicationsRequest reuse permissionsArticle Views320Altmetric-Citations270LEARN 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-Alertsclose Get e-Alerts
Development of a Drug Screening Platform Based on Engineered Heart Tissue (2010)

We developed a simple technique to construct large series of EHT and automatically evaluate contractile activity. The method shall be useful for drug screening and disease modeling.
Magnetic Resonance Imaging of Implanted Deep Brain Stimulators: Experience in a Large Series (2007)

Magnetic resonance imaging (MRI) is a commonly used and important imaging modality to evaluate lead location and rule out complications after deep brain stimulation (DBS) surgery. Recent safety concerns have prompted new safety recommendations for the use of MRI in these patients, including a new recommendation to limit the specific absorption rate (SAR) of the MRI sequences used to less than 0.1 W/kg. Following SAR recommendations in real-world situations is problematic for a variety of reasons. We review our experience scanning patients with implanted DBS systems over a 7-year period using a variety of scanning techniques and four scanning platforms. 405 patients with 746 implanted DBS systems were imaged using 1.5-tesla MRI with an SAR of up to 3 W/kg. Many of the DBS systems were imaged multiple times, for a total of 1,071 MRI events in this group of patients with no adverse events. This series strongly suggests that the 0.1 W/kg recommendation for SAR may be unnecessarily low for the prevention of MRI-related adverse events.
Hemophilia factor VIII therapy. B- and T-cell tolerance: from basic concepts to clinical practice. (2000)

Recent advances in the understanding of the mechanisms by which tolerance develops in both B- and T- cells have led to a re-appraisal of possible methods which could be applicable in clinical settings such as hemophilia patients with inhibitors. Thus, it is now clear that a number of mechanisms operate in such a way as to actively induce anergy of B- or T- cells, or even to specifically delete cells in the periphery. The characteristics inherent to the B- and T- cell repertoires and peripheral pools play a major role in the efficiency and maintenance of tolerance induction. The purpose of this manuscript is to review the mechanisms of tolerance induction briefly so as to provide a framework for the understanding of current and future attempts to achieve Factor VIII unresponsiveness in hemophilia A patients.
Inhibition of superoxide anion radical production by ebselen (PZ51) and its sulfur analogue (PZ25) in guinea pig alveolar macrophages. (1989)

The production of superoxide anion radicals by guinea pig alveolar macrophages is stimulated by the chemotactic peptide N-formylmethionyl-leucylphenylalanine and the protein kinase C activator phorbol-12-myristate-13-acetate. Both stimulations are completely and equipotently (IC50 = 20 microM) inhibited by the seleno-organic compound ebselen. As the sulfur containing analogue, which is devoid of glutathione peroxidase-like activity, shows the same inhibitory activity towards superoxide anion radical production the observed effect of ebselen can not be explained by the described glutathione peroxidase-like activity. The observed inhibition is probably caused by an inhibition of protein kinase C or inhibition at a level distal to protein kinase C activation.
Lack of efficacy of clozapine monotherapy in refractory obsessive- compulsive disorder (1995)

These findings suggest that clozapine monotherapy is not effective for most adult patients with treatment-resistant obsessive-compulsive disorder.