gebhart/patrepeval huggingface dataset:
c-myc, p53 andbcl-2, apoptosis-related genes in infiltrating breast carcinomas: Evidence of a link between bcl-2 protein over-expression and a lower risk of metastasis and death in operable patients (1999)

Apoptosis is an important physiological process controlled by multiple genes, including c-myc, p53 and bcl-2, and its inhibition may lead to the development of human cancers. In this study, we analyzed expression of the c-myc gene using Northern blot and of the p53 and bcl-2 proteins by immuno-histochemistry in 175 breast tumor specimens obtained from patients with operable breast cancer. We evaluated the relation between expression of these 3 genes and (i) the main usual prognostic factors (tumor size, histo-prognostic grade, hormone receptors and number of positive nodes); (ii) the risk of death and relapse, taking into account these 4 factors, after a mean period of follow-up of 9.5 years (SD 2 years). Over-expression of c-myc, p53 and bcl-2 was observed in 35%, 23% and 63% of tumors, respectively. Over-expression of c-myc was strongly linked to the number of positive nodes (p = 0.0005). p53 protein expression was associated with both high-grade (p = 0.0001) and hormone receptor-negative (p = 0.0001) tumors. In contrast, bcl-2 protein over-expression was associated with the main favorable prognostic factors and, more particularly, with hormone receptor-positive tumors (p = 0.0001). Multivariate analysis, using the Cox model, showed that only 2 factors were independently linked to the risk of death: number of positive nodes, which increased the risk (p = 0.0001), and bcl-2 protein over-expression, which decreased the risk (p = 0.008). When bcl-2 over-expression was studied in relation to nodal status, hormone receptor status and chemo- and hormone therapy, no significant difference was observed between different subgroups of patients. bcl-2 expression was also associated with a significantly lower risk of distant metastasis (p = 0.04). In conclusion, bcl-2 expression characterizes a particular phenotype of breast cancer with a favorable prognosis, and it may therefore be used as a marker of long-term survival. Int. J. Cancer (Pred. Oncol.) 84:562-567, 1999.
Bone Morphogenetic Protein-1 Processes Probiglycan (2000)

Bone morphogenetic protein-1 (BMP-1) is a metalloprotease that plays important roles in regulating the deposition of fibrous extracellular matrix in vertebrates, including provision of the procollagen C-proteinase activity that processes the major fibrillar collagens I-III. Biglycan, a small leucine-rich proteoglycan, is a nonfibrillar extracellular matrix component with functions that include the positive regulation of bone formation. Biglycan is synthesized as a precursor with an NH(2)-terminal propeptide that is cleaved to yield the mature form found in vertebrate tissues. Here, we show that BMP-1 cleaves probiglycan at a single site, removing the propeptide and producing a biglycan molecule with an NH(2) terminus identical to that of the mature form found in tissues. BMP-1-related proteases mammalian Tolloid and mammalian Tolloid-like 1 (mTLL-1) are shown to have low but detectable levels of probiglycan-cleaving activity. Comparison shows that wild type mouse embryo fibroblasts (MEFs) produce only fully processed biglycan, whereas MEFs derived from embryos homozygous null for the Bmp1 gene, which encodes both BMP-1 and mammalian Tolloid, produce predominantly unprocessed probiglycan, and MEFs homozygous null for both the Bmp1 gene and the mTLL-1 gene Tll1 produce only unprocessed probiglycan. Thus, all detectable probiglycan-processing activity in MEFs is accounted for by the products of these two genes.
Inhibitors in factor IX deficiency a report of the ISTH‐SSC international FIX inhibitor registry (1997–2006) (2009)

Haemophilia B is an X-linked disorder resulting in coagulation factor IX deficiency. Patients with severe deficiency (<1% factor IX activity) may have significant bleeding complications similar to patients with haemophilia A or factor VIII deficiency. The development of inhibitory antibodies to the missing coagulation factor is a major complication in patients with haemophilia. While the incidence of inhibitors in patients with haemophilia A is higher than that in haemophilia B, the occurrence of allergic and or anaphylactic reactions with the development of inhibitors is unique to haemophilia B patients. Since haemophilia B is a rare bleeding disorder and the incidence of inhibitors is an even rarer entity, a registry was established by Dr Indira Warrier under the auspices of the FVIII/FIX subcommittee of the International Society of Thrombosis and Haemostasis, to gather information on the occurrence and characteristics of patients with inhibitors and also the incidence of allergic and anaphylactic reactions in this group of patients. This is the first report from this registry and helps us to gather some insight on haemophilia B patients with inhibitors and complications related to inhibitor development and difficulties with immune tolerance.
Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p. (1996)

Anaphase initiation has been postulated to be controlled through the ubiquitin-dependent proteolysis of an unknown inhibitor. This process involves the anaphase promoting complex (APC), a specific ubiquitin ligase that has been shown to be involved in mitotic cyclin degradation. Previous studies demonstrated that in Saccharomyces cerevisiae, Pds1 protein is an anaphase inhibitor and suggested that it may be an APC target. Here we show that in yeast cells and in mitotic Xenopus extracts Pds1p is degraded in an APC-dependent manner. In addition, Pds1p is directly ubiquitinated by the Xenopus APC. In budding yeast Pds1p is degraded at the time of anaphase initiation and nondegradable derivatives of Pds1p inhibit the onset of anaphase. We conclude that Pds1p is an anaphase inhibitor whose APC-dependent degradation is required for the initiation of anaphase.
Design of a free space optical switch demonstrator for a VCSEL-based photonic packet switch (2001)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text C. A. T. H. Tee, W. A. Crossland, N. Collings, T. D. Wilkinson, and P. Robertson, "Design of a free space optical switch demonstrator for a VCSEL-based photonic packet switch," in Ultrafast Electronics and Optoelectronics, A. Sawchuk, ed., Vol. 49 of OSA Trends in Optics and Photonics (Optica Publishing Group, 2001), paper UFA7. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Immunomodulatory derivatives induce PU.1 down-regulation, myeloid maturation arrest, and neutropenia (2009)

The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide yield high response rates in patients with multiple myeloma, but the use of IMiDs in multiple myeloma is associated with neutropenia and increased risk for venous thromboembolism (VTE) by mechanisms that are unknown. We show that IMiDs down-regulate PU.1, a key transcription factor involved in granulocyte differentiation in vitro and in patients treated with lenalidomide. Loss of PU.1 results in transient maturation arrest with medullary accumulation of immature myeloid precursors and subsequent neutropenia. Accumulation of promyelocytes leads to high levels of the platelet aggregation agonist, cathepsin G stored in the azurophilic granules of promyelocytes. High levels of cathepsin G subsequently may increase the risk of VTE. To our knowledge, this is the first report investigating the underlying mechanism of IMiD-induced neutropenia and increased risk of VTE in multiple myeloma.
Multidrug resistance transporters and modulation (2000)

Multidrug resistance (MDR), whereby tumor cells simultaneously possess intrinsic or acquired cross-resistance to diverse chemotherapeutic agents, hampers the effective treatment of cancer. Molecular investigations in MDR resulted in the isolation and characterization of genes coding for several proteins associated with MDR, including P-glycoprotein (P-gp), the multidrug resistance associated protein (MRP1), the lung resistance protein (LRP), and, more recently, the breast cancer resistance protein (BCRP). These transmembrane proteins cause MDR either by decreasing the total intracellular retention of drugs or redistributing intracellular accumulation of drugs away from target organelles. These proteins are expressed at varying degrees in different neoplasms, including the AIDS-associated non-Hodgkin lymphoma and Kaposi sarcoma and are generally associated with poor prognosis. Several MDR-reversing agents are in various stages of clinical development. First-generation modulators such as verapamil, quinidine, and cyclosporin required high doses of drugs to reverse MDR and were associated with unacceptable toxicities. Second- and third-generation MDR inhibitors include PSC 833, GF120918, VX-710, and LY335979, among others. Limitations to the use of these modulators include multiple and redundant cellular mechanisms of resistance, alterations in pharmacokinetics of cytotoxic agents, and clinical toxicities. Studies to validate the role of MDR reversal in the treatment of various malignancies are underway. A potential use of these agents may be to enhance intestinal drug absorption and increase drug penetration to biologically important protective barriers, such as the blood-brain, blood-cerebrospinal fluid, and the maternal-fetal barriers. The use of MDR modulators with drugs such as the antiviral protease inhibitors and cytotoxics may enhance drug accumulation in sanctuary sites that are traditionally impenetrable to these agents.
Localization and Regulation of the ATP6V0A4 (a4) Vacuolar H+-ATPase Subunit Defective in an Inherited Form of Distal Renal Tubular Acidosis (2003)

Vacuolar-type H(+)-ATPases (V-H(+)-ATPases) are the major H(+)-secreting protein in the distal portion of the nephron and are involved in net H(+) secretion (bicarbonate generation) or H(+) reabsorption (net bicarbonate secretion). In addition, V-H(+)-ATPases are involved in HCO(3)(-) reabsorption in the proximal tubule and distal tubule. V-H(+)-ATPases consist of at least 13 subunits, the functions of which have not all been elucidated. Mutations in the accessory ATP6V0A4 (a4 isoform) subunit have recently been shown to cause an inherited form of distal renal tubular acidosis in humans. Here, the localization of this subunit in human and mouse kidney was studied and the regulation of expression and localization of this subunit in mouse kidney in response to acid-base and electrolyte intake was investigated. Reverse transcription-PCR on dissected mouse nephron segments amplified a4-specific transcripts in proximal tubule, loop of Henle, distal convoluted tubule, and cortical and medullary collecting duct. a4 protein was localized by immunohistochemistry to the apical compartment of the proximal tubule (S1/S2 segment), the loop of Henle, the intercalated cells of the distal convoluted tubule, the connecting segment, and all intercalated cells of the entire collecting duct in human and mouse kidney. All types of intercalated cells expressed a4. NH(4)Cl or NaHCO(3) loading for 24 h, 48 h, or 7 d as well as K(+) depletion for 7 and 14 d had no influence on a4 protein expression levels in either cortex or medulla as determined by Western blotting. Immunohistochemistry, however, demonstrated a subcellular redistribution of a4 in response to the different stimuli. NH(4)Cl and K(+) depletion led to a pronounced apical staining in the connecting segment, cortical collecting duct, and outer medullary collecting duct, whereas NaHCO(3) loading caused a stronger bipolar staining in the cortical collecting duct. Taken together, these results demonstrate a4 expression in the proximal tubule, loop of Henle, distal tubule, and collecting duct and suggest that under conditions in which increased V-H(+)-ATPase activity is required, a4 is regulated by trafficking but not protein expression. This may allow for the rapid adaptation of V-H(+)-ATPase activity to altered acid-base intake to achieve systemic pH homeostasis. The significance of a4 expression in the proximal tubule in the context of distal renal tubular acidosis will require further clarification.
Interleukin-17 gene expression in patients with rheumatoid arthritis (2007)

Interleukin-17 is a proinflammatory cytokine. Recent animal studies have shown that IL-17 plays a role in the initiation and progression of arthritis. However, whether IL-17 has a prominent role in human rheumatoid arthritis (RA) or not remains unclear. Here we investigated the role of IL-17 in patients with RA. cDNA was prepared from knee joint synovial tissues of RA (n = 11) and osteoarthritic (OA, n = 10) patients and PBMC of RA (n = 52) and healthy subjects (n = 34). IL-17 gene expression level was measured by real-time PCR, and was compared with various clinical parameters. IL-17 gene expression in synovial tissues of RA was similar to that in OA. IL-17 gene expression level in PBMC of RA patients was significantly higher than in the control. The response (changes in DAS) to two-week treatment with anti-TNF-alpha blockers (infliximab or etanercept) did not correlate with changes in IL-17 gene expression levels. The IL-17/TNF-alpha gene expression ratio at baseline (before treatment) tended to be lower in responders to the treatment. Expression of IL-17 gene in PBMC may be associated with the inflammatory process of RA. IL-17/TNF-alpha expression ratio is a potentially suitable marker of response to anti-TNF-alpha therapy.
Bile Salts and Glycine as Cogerminants for Clostridium difficile Spores (2008)

Spore formation by Clostridium difficile is a significant obstacle to overcoming hospital-acquired C. difficile-associated disease. Spores are resistant to heat, radiation, chemicals, and antibiotics, making a contaminated environment difficult to clean. To cause disease, however, spores must germinate and grow out as vegetative cells. The germination of C. difficile spores has not been examined in detail. In an effort to understand the germination of C. difficile spores, we characterized the response of C. difficile spores to bile. We found that cholate derivatives and the amino acid glycine act as cogerminants. Deoxycholate, a metabolite of cholate produced by the normal intestinal flora, also induced germination of C. difficile spores but prevented the growth of vegetative C. difficile. A model of resistance to C. difficile colonization mediated by the normal bacterial flora is proposed.
Human cellular fps/fes cDNA rescued via retroviral shuttle vector encodes myeloid cell NCP92 and has transforming potential. (1988)

We have generated a cDNA copy of human c-fps/fes from a 13 kb genomic DNA by means of a retroviral shuttle vector, and have begun characterization of its biological and biochemical properties. The cDNA was able to direct the in vitro synthesis of a protein that was indistinguishable from myeloid cell c-fps/fes NCP92 by immunoprecipitation with specific antisera, electrophoretic mobility, tryptic fingerprint analysis, and its associated protein kinase activity. When the coding sequence of the gag-v-fps/fes P108 fusion protein in Gardner Arnstein Feline sarcoma virus was substituted with the recovered cDNA, the recombinant plasmid directed the expression of NCP92 in NIH 3T3 cells but no morphological transformation was observed. By contrast, when viral gag sequences were linked to the N-terminus of NCP92, the chimeric gene induced foci of transformed cells. These transformants were capable of anchorage independent growth, were tumorigenic in nude mice, and expressed a gag fusion protein kinase of high specific activity. The biological properties of this recombinant are discussed. We conclude that normal human c-fps/fes can be activated by N-terminal linkage to gag.
Kallikrein—Kinin System in One- and Two-Kidney Goldblatt Hypertensive Rats (1979)

1. Urinary kallikrein, renal tissue kininogenase activity, and plasma kininogen were measured during the development of hypertension in rats, either with left renal artery clamped and contralateral kidney intact (Goldblatt 2-kidney) or removed (Goldblatt 1-kidney). Plasma urea, plasma volume and blood volume were also measured. 2. In Goldblatt 2-kidney rats, urinary kallikrein was not significantly different from that of sham-operated rats up to the 5th post-operative week even though at this time the Goldblatt 2-kidney animals were hypertensive. Urinary kallikrein started to decrease at week 8. Plasma kininogen was significantly elevated 5 and 10 weeks after surgery and returned to normal by week 15. No changes in renal tissue kininogenase activity were observed. Plasma urea and plasma and blood volumes were normal 5 weeks after, but significantly increased at 10 and 15 weeks after surgery. 3. In Goldblatt 1-kidney rats from the fifth week urinary kallikrein and renal kininogenase activity were significantly decreased compared with unilaterally nephrectomized rats, whereas plasma kininogen, plasma urea and plasma and blood volumes were significantly elevated. 4. These results show important differences in the kallikrein system between the Goldblatt 1-kidney and 2-kidney models of renovascular hypertension in rats.
Gold and Silver Nanoparticles Functionalized by the Adsorption of Dialkyl Disulfides (1998)

The formation of three-dimensional self-assembled monolayers (3-D SAMs) generated by the adsorption of <i>n</i>-octadecyl disulfide onto colloidal gold and silver nanoparticles is described. The functionalized nanoparticles were characterized by solubility, transmission electron microscopy, ultraviolet-visible spectroscopy, <sup>1</sup>H nuclear magnetic resonance spectroscopy, surface-enhanced Raman spectroscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. On gold nanoparticles, this new functionalization method affords crystalline 3-D SAMs that are indistinct from those prepared by the analogous adsorption of <i>n</i>-octadecanethiol. On silver nanoparticles, however, the films derived from <i>n</i>-octadecyl disulfide appear to be somewhat less crystalline than those prepared similarly from <i>n</i>-octadecanethiol. The origin of this difference is briefly explored and discussed.
The neurodevelopmental hypothesis of schizophrenia: Following a trail of evidence fromcradle to grave (2000)

This is a critical review of the literature related to the neurodevelopmental hypothesis of schizophrenia which posits that the illness is related to abnormal brain development. The review focuses on data deriving from clinical studies, and it is organized according to the life phase from which the data were collected: conception and birth, infancy and childhood up to the onset of the illness, after illness onset, and postmortem. The neurodevelopmental hypothesis is supported by several pieces of evidence, including increased frequency of obstetric complications in patients with schizophrenia: the presence of minor physical anomalies; the presence of neurological, cognitive, and behavioral dysfunction long before illness onset; a course and outcome of the illness itself that is incompatible in most cases with a degenerative illness; the stability of brain structural measures over time; and the absence of postmortem evidence of neurodegeneration. A historical perspective on how this research accumulated and a section addressing important areas of future investigation are also provided. We conclude that schizophrenia is certainly not a degenerative brain disorder, and that it is likely that a brain insult in utero or at birth plays a role in its expression. Current evidence cannot completely exclude the role of environmental variables after birth. In addition, it is possible that other psychiatric disorders may also have a neurodevelopmental component.
Tefsir Çalışmalarında Kur'an Meseleleri ve Atasözlerimiz (2015)

This article, argues the similarity between sacred texts and proverbs. This proverbs are basic component of all nation thoughts and cultures. They are also the main method of communication between them and the systematic thought and knowledge of all people on the world. But in this paper was discussed Turkish proverbs only. The purpose of Quran interpretation is to explain the reveluation basic means. When the people understand this means the best of all with addition knowledge and with proverbial explanation, thus the commentators and explainers -in their translating/willful misinterpretation works- must connected with these proverbs and religious texts as a translation method
Zoonoses in Solid-Organ and Hematopoietic Stem Cell Transplant Recipients (2007)

Numerous reports exist of the transmission of zoonoses to humans during and after solid-organ and hematopoietic stem cell transplantation. Donor-derived infections of numerous etiologies, including West Nile virus infection, Chagas disease, toxoplasmosis, rabies, lymphocytic choriomeningitis virus infection, and infection due to Brucella species have been reported. Most zoonoses occur as a primary infection after transplantation, and immunocompromised patients are more likely to experience significant morbidity and mortality from these infections. Risks of zoonotic infection in the posttransplantation period could be reduced by patient education. Increased recognition of the risks of zoonoses, as well as the advent of molecular biology-based testing, will potentially augment diagnostic aptitude. Documented zoonotic infection as it affects transplantation will be the primary focus of this review.
The Synthetic Triterpenoids CDDO-Methyl Ester and CDDO-Ethyl Amide Prevent Lung Cancer Induced by Vinyl Carbamate in A/J Mice (2007)

We report the first use of new synthetic triterpenoids to prevent lung cancer in experimental animals. Female A/J mice were treated with the mutagenic carcinogen vinyl carbamate, which induces adenocarcinoma of the lung in all animals within 16 weeks. If mice were fed either the methyl ester or the ethyl amide derivative of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-ME and CDDO-EA, respectively), beginning 1 week after dosing with carcinogen, the number, size, and severity of lung carcinomas were markedly reduced. The mechanisms of action of CDDO-ME and CDDO-EA that are germane to these in vivo findings are the following results shown here in cell culture: (a) suppression of the ability of IFN-gamma to induce de novo formation of nitric oxide synthase in a macrophage-like cell line RAW264.7, (b) induction of heme oxygenase-1 in these RAW cells, and (c) suppression of phosphorylation of the transcription factor signal transducers and activators of transcription 3 as well as induction of apoptosis in human lung cancer cell lines.
Navigation Errors Introduced By Ground Vehicle Dynamics (2005)

An analysis of navigational accuracy when influenced by ground vehicle dynamics is presented. Tests beds outfitted with various sensor suites were used to collect data when normal and extreme driving maneuvers are executed. The data was run through an extended Kalman filter to produce a navigation solution. The Kalman filter inputs varied on each test bed, using both automotive and tactical grade Inertial Measurement Units (IMU). The position, velocity, and course measurements were obtained from a DGPS unit mounted on the vehicles and used as a truth measurement when exploring dead reckoning error. Additional measurements, such as wheel speed, radar speed, and magnetometer heading, were added to improve the robustness and reliability of the solution. The results of the work show the effect of both longitudinal and lateral vehicle slip on the navigation solution. In addition, the attempt of the various sensors to correct the errors is investigated.