gebhart/patrepeval huggingface dataset:
Evidence that platelet and tumour heparanases are similar enzymes (1999)

In order to enter tissues, blood-borne metastatic tumour cells and leucocytes need to extravasate through the vascular basal lamina (BL), a process which involves a battery of degradative enzymes. A key degradative enzyme is the endoglycosidase heparanase, which cleaves heparan sulphate (HS), an important structural component of the vascular BL. Previously, tumour-derived heparanase activity (which has been shown to be related to the metastatic potential of murine and human melanoma cell lines) was reported to cleave HS and be inhibited by heparin, as distinct from human platelet heparanase, which cleaved both substrates [Nakajima, Irimura and Nicolson (1988) J. Cell Biochem. 36, 157-167]. We recently reported the purification of human platelet heparanase and showed that the enzyme is a 50-kDa endoglucuronidase [Freeman and Parish (1998) Biochem. J. 330, 1341-1350]. We now report the purification and characterization of heparanase activity from highly metastatic rat 13762 MAT mammary adenocarcinoma and human HCT 116 colonic carcinoma cells and from rat liver using essentially the same procedure that was reported for purification of the human platelet enzyme. The rat 13762 MAT tumour enzyme, which has a native M(r) of 45 kDa when analysed by gel-filtration chromatography and by SDS/PAGE, was observed to be an endoglucuronidase that degraded heparin and HS to fragments of the same sizes as the human platelet enzyme does. N-deglycosylation of both the human platelet and rat 13762 MAT tumour enzymes gave, in each case, a 41-kDa band by SDS/PAGE analysis, demonstrating that the observed difference in M(r) between the platelet and tumour enzymes may have been due largely to differences in the relative amounts of N-glycosylation. Two peptides were isolated following Endoproteinase Lys-C digestion of both the human platelet and rat 13762 MAT tumour heparanases and were shown to be highly similar. Both the rat liver and human colonic carcinoma heparanases also degraded both heparin and HS to fragments of the same sizes as the human platelet enzyme does. Western-blot analysis of an SDS/PAGE gel using antibodies raised against human platelet heparanase demonstrated that human platelet, human tumour and rat tumour heparanases were immunochemically cross-reactive. In conclusion, because of the similarities in their sizes, substrate specificities, peptide sequences and immunoreactivities, we propose that heparanase activities present in human platelets, rat liver and in rat and human tumour cells are, in fact, mediated by a similar enzyme.
Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats (2007)

This study indicates that a neural prosthetic device based on pudendal nerve stimulation might be developed to restore micturition function for people with SCI.
Toll-Like Receptor 4 Activation in Cancer Progression and Therapy (2011)

Cancer immunotherapy has been the focus of intense research since the late 19th century when Coley observed that bacterial components can contribute to cancer regression by eliciting an antitumor immune response. Successful activation and maturation of tumor-specific immune cells is now known to be mediated by bacterial endotoxin, which activates Toll-like receptor 4 (TLR4). TLR4 is expressed on a variety of immune as well as tumor cells, but its activation can have opposing effects. While TLR4 activation can promote antitumor immunity, it can also result in increased tumor growth and immunosuppression. Nevertheless, TLR4 engagement by endotoxin as well as by endogenous ligands represents notable contribution to the outcome of different cancer treatments, such as radiation or chemotherapy. Further research of the role and mechanisms of TLR4 activation in cancer may provide novel antitumor vaccine adjuvants as well as TLR4 inhibitors that could prevent inflammation-induced carcinogenesis.
The Role of the Carbohydrate Response Element-Binding Protein in Male Fructose-Fed Rats (2012)

By 2030, nearly half of Americans will have nonalcoholic fatty liver disease. In part, this epidemic is fueled by the increasing consumption of caloric sweeteners coupled with an innate capacity to convert sugar into fat via hepatic de novo lipogenesis. In addition to serving as substrates, monosaccharides also increase the expression of key enzymes involved in de novo lipogenesis via the carbohydrate response element-binding protein (ChREBP). To determine whether ChREBP is a potential therapeutic target, we decreased hepatic expression of ChREBP with a specific antisense oligonucleotide (ASO) in male Sprague-Dawley rats fed either a high-fructose or high-fat diet. ChREBP ASO treatment decreased plasma triglyceride concentrations compared with control ASO treatment in both diet groups. The reduction was more pronounced in the fructose-fed group and attributed to decreased hepatic expression of ACC2, FAS, SCD1, and MTTP and a decrease in the rate of hepatic triglyceride secretion. This was associated with an increase in insulin-stimulated peripheral glucose uptake, as assessed by the hyperinsulinemic-euglycemic clamp. In contrast, ChREBP ASO did not alter hepatic lipid content or hepatic insulin sensitivity. Interestingly, fructose-fed rats treated with ChREBP ASO had increased plasma uric acid, alanine transaminase, and aspartate aminotransferase concentrations. This was associated with decreased expression of fructose aldolase and fructokinase, reminiscent of inherited disorders of fructose metabolism. In summary, these studies suggest that targeting ChREBP may prevent fructose-induced hypertriglyceridemia but without the improvements in hepatic steatosis and hepatic insulin responsiveness.
Nicotine effects on PGE2 and IL‐1β release by LPS‐treated human monocytes (1996)

Cigarette smoking is a major risk factor in the development and further progression of periodontitis. However, little is known regarding the pathogenesis of smoking-related periodontal diseases. The purpose of this study was to examine the effects of nicotine, alone and in combination with lipopolysaccharide (LPS), on monocyte secretion of bone-resorbing factors, PGE2 and IL-1 beta. Peripheral blood monocytes (PBM) were isolated by counterflow centrifugal elutriation from 15 healthy, non-smoking donors. PBM were incubated for 24 h in RPMI 1640 containing nicotine (0, 50 ng/ml, 1 microgram/ml, 10 micrograms/ml and 100 micrograms/ml) with or without 10 micrograms/ml Porphyromonas gingivalis LPS or Escherichia coli LPS. Culture supernatants were assayed for PGE2 and IL-1 beta by ELISA. None of the nicotine preparations resulted in significant PBM secretion of PGE2 and IL-1 beta above that of unstimulated cultures. However, PGE2 release was potentiated 1.7-fold by the combination of P. gingivalis LPS and 10 micrograms/ml nicotine relative to P. gingivalis LPS alone (p < 0.05, one-way ANOVA). Prostaglandin E2 release also was potentiated 3.5-fold by P. gingivalis LPS and 100 micrograms/ml nicotine relative to P. gingivalis LPS alone (p < 0.00001, one-way ANOVA) and 3.1-fold by E. coli LPS and 100 micrograms/ml nicotine relative to E. coli LPS alone (p < 0.00001, one-way ANOVA). IL-1 beta secretion was lower for either LPS plus 100 micrograms/ml nicotine relative to LPS alone, although not significantly. These data demonstrate upregulation of LPS-mediated monocyte secretion of PGE2 by nicotine and suggest a potential role for nicotine in periodontal disease pathogenesis.
Inhibition of Intrahepatic Gamma Interferon Production by Hepatitis C Virus Nonstructural Protein 5A in Transgenic Mice (2009)

Hepatitis C virus (HCV) utilizes strategies to suppress or evade the host immune response for establishment of persistent infection. We have shown previously that HCV nonstructural protein 5A (NS5A) impairs tumor necrosis factor alpha (TNF-alpha)-mediated apoptosis. In this study, we have examined the immunomodulatory role of HCV NS5A protein in transgenic mouse (NS5A-Tg) liver when mice were challenged with an unrelated hepatotropic adenovirus as a nonspecific stimulus. Hepatotropic adenovirus was introduced intravenously into NS5A-Tg mice and control mice, and virus clearance from liver was compared over a time course of 3 weeks. The differential mRNA expression levels of 84 cytokine-related genes, signal pathway molecules, transcription factors, and cell surface molecules were determined using real-time reverse transcription-PCR array. NS5A-Tg mice failed to clear adenovirus from liver up to 3 weeks postinfection while control mice cleared virus within 1 to 2 weeks. Subsequent study revealed that gamma interferon (IFN-gamma) expression is inhibited at both the mRNA and protein levels in NS5A-Tg mice, and an inverse expression of transcription factors Gata-3 and Tbx21 is observed. However, TNF-alpha mRNA and protein expression were elevated in both NS5A-Tg and control mice. Together, our results suggested that HCV NS5A acts as an immunomodulator by inhibiting IFN-gamma production and may play an important role toward establishment of chronic HCV infection.
[Sorption properties of carboxyl cation exchangers with a bacteriostatic effect]. (1981)

Sorption properties of new carboxyl cation exchangers containing components of salicylic acid (CST and CMTS) and benzoic acid (CBT and CMTB) were examined with respect to large organic ions. Such cation exchangers were shown to have greater permeability for high molecular weight proteins that sorbents of the Biocarb type. Bacteriostatic properties of the above cation exchangers were studied. With an increase in the content of the bactericidal component the bacteriostatic effect of the cation exchangers on Escherichia coli and Staphylococcus aureus enhanced. The cation exchangers CST and CMTS showed a greater bacteriostatic effect than those CBT and CMTB.
Glycosaminoglycan fractions from human arteries presenting diverse susceptibilities to atherosclerosis have different binding affinities to plasma LDL. (1994)

The topographic distribution of atherosclerotic lesions is influenced by biochemical factors intrinsic to the arterial wall. In the present work we have investigated whether the composition/chemical structure of glycosaminoglycans constitutes one of these factors. Normal human arteries were obtained at necropsy, and in order of decreasing susceptibility to atherosclerosis, consisted of the abdominal and thoracic aortas and the iliac and pulmonary arteries. The results showed similar concentrations of total glycosaminoglycan and collagen. Of the glycosaminoglycans known to interact with low-density lipoprotein (LDL), dermatan sulfate was present in all arteries in comparable concentrations, but the aortas had a 30% higher content of chondroitin 4/6-sulfate, which in turn was slightly enriched in 6-sulfated disaccharide units. LDL-affinity chromatography with dermatan sulfate+chondroitin 4/6-sulfate fractions demonstrated that increasing affinity to LDL matched an increasing susceptibility to atherosclerosis. Analysis of glycosaminoglycans in the eluates indicated a positive correlation between affinity to LDL and increasing molecular weight and the existence of a fraction of glycosaminoglycans of high affinity to LDL in the aortas only. These results suggest that arterial glycosaminoglycans participate in the multifactorial mechanisms that modulate the differential localization of atherosclerotic lesions.
Transverse-mode stabilised 630 nm-band AlGaInP strained multiquantum-well laser diodes grown on misoriented substrates (1992)

Transverse-mode stabilised AlGaInP (γL = 638 nm) compressively strained multiquantum-well laser diodes have been successfully fabricated by MOCVD using (100) GaAs substrates with a misorientation of 7° towards the (011) direction. The maximum CW operation temperature was 60°C, which is the highest value for 630 nm-band AlGalnP lasers so far. These lasers operated for more than 2000 h without significant degradation under 3 mW at 40°C.
Radioimmunotherapy of Breast Cancer Metastases with α-Particle Emitter 225Ac: Comparing Efficacy with 213Bi and 90Y (2009)

alpha-Particles are suitable to treat cancer micrometastases because of their short range and very high linear energy transfer. alpha-Particle emitter (213)Bi-based radioimmunotherapy has shown efficacy in a variety of metastatic animal cancer models, such as breast, ovarian, and prostate cancers. Its clinical implementation, however, is challenging due to the limited supply of (225)Ac, high technical requirement to prepare radioimmunoconjugate with very short half-life (T(1/2) = 45.6 min) on site, and prohibitive cost. In this study, we investigated the efficacy of the alpha-particle emitter (225)Ac, parent of (213)Bi, in a mouse model of breast cancer metastases. A single administration of (225)Ac (400 nCi)-labeled anti-rat HER-2/neu monoclonal antibody (7.16.4) completely eradicated breast cancer lung micrometastases in approximately 67% of HER-2/neu transgenic mice and led to long-term survival of these mice for up to 1 year. Treatment with (225)Ac-7.16.4 is significantly more effective than (213)Bi-7.16.4 (120 microCi; median survival, 61 days; P = 0.001) and (90)Y-7.16.4 (120 microCi; median survival, 50 days; P < 0.001) as well as untreated control (median survival, 41 days; P < 0.0001). Dosimetric analysis showed that (225)Ac-treated metastases received a total dose of 9.6 Gy, significantly higher than 2.0 Gy from (213)Bi and 2.4 Gy from (90)Y. Biodistribution studies revealed that (225)Ac daughters, (221)Fr and (213)Bi, accumulated in kidneys and probably contributed to the long-term renal toxicity observed in surviving mice. These data suggest (225)Ac-labeled anti-HER-2/neu monoclonal antibody could significantly prolong survival in HER-2/neu-positive metastatic breast cancer patients.
The effect of increased yeast alcohol acetyltransferase and esterase activity on the flavour profiles of wine and distillates (2006)

The fruity odours of wine are largely derived from the synthesis of esters and higher alcohols during yeast fermentation. The ATF1- and ATF2-encoded alcohol acetyltransferases of S. cerevisiae are responsible for the synthesis of ethyl acetate and isoamyl acetate esters, while the EHT1-encoded ethanol hexanoyl transferase is responsible for synthesizing ethyl caproate. However, esters such as these might be degraded by the IAH1-encoded esterase. The objectives of this study were: (a) to overexpress the genes encoding ester-synthesizing and ester-degrading enzymes in wine yeast; (b) to prepare Colombard table wines and base wines for distillation using these modified strains; and (c) to analyse and compare the ester concentrations and aroma profiles of these wines and distillates. The overexpression of ATF1 significantly increased the concentrations of ethyl acetate, isoamyl acetate, 2-phenylethyl acetate and ethyl caproate, while the overexpression of ATF2 affected the concentrations of ethyl acetate and isoamyl acetate to a lesser degree. The overexpression of IAH1 resulted in a significant decrease in ethyl acetate, isoamyl acetate, hexyl acetate and 2-phenylethyl acetate. The overexpression of EHT1 resulted in a marked increase in ethyl caproate, ethyl caprylate and ethyl caprate. The flavour profile of the wines and distillates prepared using the modified strains were also significantly altered as indicated by formal sensory analysis. This study offers prospects for the development of wine yeast starter strains with optimized ester-producing capability that could assist winemakers in their effort to consistently produce wine and distillates such as brandy to definable flavour specifications and styles.
임산부에서 Hepatitis C Virus 감염에 관한 연구 (2000)

목적: 임산부에서 C형 간염의 유병율 및 위험인자를 알아보고, C형 간염이 임산부와 신생아에 미칠 수 있는 영향을 알아보기 위한 기본적인 자료가 되고자 본 연구를 시행하였다. 연구방법: 1997년 3월부터 1998년 2월까지 본 병원에서 임신 20주 이상 분만한 산모 5655명을 대상으로 통상적인 HCV-Ab검사(RIA)를 시행하였다. HCV-Ab 양성인 경우의 대부분에서 PCR을 통한 HCV-RNA 검사를 실시하였으며, C형간염의 위험인자라고 생각되는 요인에 대한 조사와 분만시 산모와 신생아의 간기능과 HCV-Ab 양성율에 대하여 조사하였다. 결과: 5655명의 임산부 중 25명의 산모에서 HCV-Ab 양성을 보여 0.44%의 유병율을나타내었다. 그 중 20예에서 HCV-RNA 검사를 시행하였고, 12예(60%)에서 HCV-RNA 양성이었다. C형간염의 위험인자로는 습관성 정맥용 약물사용자, 흡연의 기왕력, 임신 중의 습관성 음주, 간경화 등이 의의있는 것으로 나타났고, 수혈의 기왕력, 매독, B형 바이러스 간염 보균 등의 인자는 HCV-Ab 양성군과 HCV-Ab 음성군간에 큰 차이를 보이지 않았다.
분만시 임산부의 간기능 수치는 HCV-Ab 양성군에서 의의 있게 비정상을 보였으나 입원기간의 연장같은 치료를 필요로 하지는 않았다. 신생아의 경우에는 HCV-Ab 양성군과 음성군사이에 의의있는 간기능검사 수치이상은 보이지 않았다. 또한 HCV-Ab 양성인 산모의 신생아 중 20예에서 분만시 HCV-Ab 검사를 실시, 20예에서 양성을 보였으나, 그 중 2예에서만(10%) HCV-RNA 양성을 나타내었다. 결론: 연구결과 우리나라 산모에서 C형바이러스 간염의 유병율은 B형 바이러스 간염과 비교하여 많지 않으나 습관성 정맥용 약물 사용자나 간경화가 있는 경우, 음주, 흡연 등의 위험인자가 있는 경우에는 꼭 HCV-Ab 검사와 정량적 HCV-RNA 검사를 시행하여 간질환의 만성화와 태아로의 수직감염의 가능성에 대비하여야 하겠다.
Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesisin vivo (2000)

Field cancerization predisposes the upper aerodigestive tract mucosa to the formation of multiple primary tumors, when exposed to environmental carcinogens. Up-regulation of epidermal growth factor receptor occurs early in squamous cell carcinogenesis and is critical for the loss of growth control in a variety of human cancers, including head and neck squamous cell carcinomas. In these tumor cells in culture, epidermal growth factor receptor stimulation initiates signaling via persistent activation of selective STAT proteins. To determine the timing of Stat3 activation in head and neck carcinogenesis, we studied the expression and constitutive activation of Stat3 in tumors and normal mucosa from patients with head and neck cancer compared with mucosa from controls without cancer. Stat3 was up-regulated and constitutively activated in both primary human head and neck tumors as well as in normal mucosa from these cancer patients compared with control normal mucosa from patients without cancer. In vivo liposome-mediated gene therapy with a Stat3 antisense plasmid efficiently inhibited Stat3 activation, increased tumor cell apoptosis, and decreased Bcl-x(L) expression in a head and neck xenograft model. These findings provide evidence that constitutively activated Stat3 is an early event in head and neck carcinogenesis that contributes to the loss of growth control by an anti-apoptotic mechanism.
Deriving marketing intelligence from online discussion (2005)

Weblogs and message boards provide online forums for discussion that record the voice of the public. Woven into this mass of discussion is a wide range of opinion and commentary about consumer products. This presents an opportunity for companies to understand and respond to the consumer by analyzing this unsolicited feedback. Given the volume, format and content of the data, the appropriate approach to understand this data is to use large-scale web and text data mining technologies.This paper argues that applications for mining large volumes of textual data for marketing intelligence should provide two key elements: a suite of powerful mining and visualization technologies and an interactive analysis environment which allows for rapid generation and testing of hypotheses. This paper presents such a system that gathers and annotates online discussion relating to consumer products using a wide variety of state-of-the-art techniques, including crawling, wrapping, search, text classification and computational linguistics. Marketing intelligence is derived through an interactive analysis framework uniquely configured to leverage the connectivity and content of annotated online discussion.
Effects of Vasoactive Drugs on Circulation in Canine Subcutaneous Adipose Tissue (1970)

Abstract The circulatory effects of acetylcholine, bradykinin, isoprenaline, histamine, 5‐hydroxytrypt‐amine (5‐HT), noradrenaline and prostaglandin Ei (PGE 1 ) were studied in the canine subcutaneous adipose tissue. PGE 1 produced clearcut vasodilatations at calculated blood concentrations as low as 10 ‐9 M and was found to be the most potent of the drugs tested. PGE 1 was about 1000 times more potent than acetylcholine and about 10 times more potent than histamine. 5‐HT induced a moderate blood flow increase with no change or a decrease of tissue volume, indicating a constriction of the venous section. The vascular responses to noradrenaline infusions were essentially similar to those produced by sympathetic nerve activation, i.e . constriction of arterioles and veins and a markedly increased capillary filtration coefficient (CFC). Histamine and bradykinin induced increases of CFC of the same magnitude as did sympathetic nerve stimulation, whereas acetylcholine, isoprenaline, 5‐HT and PGE 1 induced smaller increases of CFC. Sympathetic nerve stimulation superimposed upon infusions of the latter drugs produced a further marked increase of CFC, while nerve stimulation applied during a period of histamine or bradykinin infusion produced no further rise or even a decrease of CFC. It is discussed that the pronounced CFC increase during sympathetic nerve stimulation is due to an increased permeability of the capillary membrane.
Effect of Topical Ophthalmic Epinastine and Olopatadine on Tear Volume in Mice (2006)

Topical epinastine did not inhibit tear secretion, whereas olopatadine caused a significant decrease in tear volume. Because of its neutral impact on the lacrimal functional unit, epinastine may be an especially good choice for the treatment of allergic conjunctivitis in patients with dry eye disease or in those who are at risk for developing dry eye.
Molekulare und klinische Auswirkungen einer Hochdruckbehandlung von allergenen Lebensmitteln (2003)

Zur Untersuchung des Einflusses einer Hochdruckbehandlung auf die Allergenitat von Lebensmitteln wurden verschiedene Lebensmittel, deren Allergene Birkenpollen assoziiert sind, ausgewahlt. Die Auswahl umfasste Haselnuss, Karotte, Kirsche, Pfirsich, Sellerie und Apfel. Native und hochdruckbehandelte Lebensmittelproben (300 und 600 MPa bei funfminutiger Haltezeit) wurden mittels Prick to Prick-Test am allergischen Patienten getestet. In vielen Fallen konnte eine Reduktion der Allergenitat durch die Hochdruckbehandlung verzeichnet werden, die mit groser Wahrscheinlichkeit auf eine Veranderung Bet v 1-homologer Allergene zuruckzufuhren ist. Die Allergenitat einiger Minorallergene scheint durch Druck nicht reduzierbar zu sein, was bei entsprechend sensibilisierten Patienten zu positiven Reaktionen im Prick to Prick-Test trotz vorangegangener Hochdruckbehandlung des Lebensmittels fuhrte.Die Reduktion der Allergenitat wurden am Beispiel des Apfels und seines Majorallergens Mal d 1 klinisch-experimentell und in vitro eingehend untersucht. Die Ergebnisse der Pricktests wurden durch orale Provokationstests auf ihre klinische Relevanz uberpruft. 19 von 19 Apfelallergikern tolerierten hochdruckbehandelten Apfel bei einer placebokontrollierten verblindeten Provokation ohne Beschwerden. Eingehende Prick to Prick-Tests zeigten, dass die Inaktivierung der Allergene mit der Druckhohe korreliert.Rekombinant hergestelltes Mal d 1 wurde in einem neutralen Puffer gelost und in die native Konformation uberfuhrt. Diese Allergenlosung wurde nativ und hochdruckbehandelt spektroskopisch untersucht. CD-Spektren und FTIR-Spektren belegen eine hochdruckinduzierte Veranderung der Proteinstruktur.