gebhart/patrepeval huggingface dataset:
Treating cancer cachexia to treat cancer (2011)

Skeletal muscle wasting is a major component of cachectic states found in a variety of disease settings, including cancer. As increasing caloric intake often provides little benefit in combating muscle loss in cachectic patients, a major research focus has been to develop strategies stimulating muscle anabolic pathways - in an attempt to fight the catabolic pathways induced during cachexia. Two recent papers have reported the beneficial effects of blocking the myostatin/activin signalling pathway in mouse models of cancer cachexia. We discuss the implications of their findings both with respect to the role that this signalling pathway may play in the aetiology of cachexia and with respect to the prospects for targeting this pathway as a therapeutic strategy in patients with cachexia.
Polyisobutylene‐based polyurethanes. V. Oxidative‐hydrolytic stability and biocompatibility (2010)

Abstract The oxidative/hydrolytic stability of polyurethanes (PUs) containing exclusively polyisobutylene (PIB), or mixed PIB/polytetramethylene oxide (PTMO), or mixed PIB/polyhexamethylene carbonate (PC) soft segments was investigated. The tensile strengths and elongations of various PUs were determined before and after agitating in 35% HNO 3 or 20% H 2 O 2 /0.1 M CoCl 2 solutions and retentions were quantified. The presence of PIB imparts significant oxidative/hydrolytic resistance. The tensile strength and elongation of PUs containing 70% PIB, or those of mixed PIB/PC soft segments with 50% PIB, remained essentially unchanged upon exposure to HNO 3 ; in contrast, PUs containing mixed PIB/PTMO soft segments with 50% PIB underwent significant degradation. The tensile strength of PUs with mixed PIB/PC (60/10%) soft segment increased after exposure to HNO 3 , most likely because of oxidative crosslinking of PC segments. PIB/PTMO‐ and PIB/PC‐based PUs and commercially available PUs (Elast‐Eon® and Carbothane®) were exposed to H 2 O 2 /CoCl 2 solutions for up to 14 weeks. Although the experimental PIB/PC‐based PUs exhibited negligible change in mechanical properties and no surface damage, Elast‐Eon® and Carbothane® showed significant surface damage. PIB‐based polyureas and Bionate® were implanted in rats for 4 weeks in vivo , and their biocompatibility was investigated. The biocompatibility of PIB‐based materials was superior to Bionate®. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2194–2203, 2010
Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma. (1996)

We assessed the therapeutic benefits of 131I treatment in patients with distant metastases of differentiated thyroid carcinoma.Of 2200 patients treated for differentiated thyroid carcinoma at our institution, 394 had lung and/or bone metastases.Two-thirds of the patients had 131I uptake in their metastases, but only 46% achieved a complete response. Prognostic factors for complete response were: younger age, presence of 131I uptake in the metastases and small extent of disease. The survival rate was 33% at 15 yr. As shown by multivariate analysis, favorable prognostic factors for survival were: younger age and time of metastases detection, well-differentiated histologic type of the thyroid tumor, presence of 131I type uptake in the metastases, small extent of the disease and year of discovery of metastases.In terms of survival, the benefits of 131I therapy cannot be demonstrated by prospective controlled studies. The present study clearly demonstrates, however, that treatment with 131I is one of the factors which accounts for survival; patients whose metastases concentrated 131I and who could be treated with radioiodine had higher survival rates. Patients who achieved complete response following treatment of distant metastases had a 15-yr survival rate of 89%, while those who did not achieve complete response had a survival rate of only 8%. The survival rate improved with the year of discovery of distant metastases, after 131I total-body imaging and serum thyroglobulin measurements were routinely used.
miR-497 and miR-34a retard lung cancer growth by co-inhibiting cyclin E1 (CCNE1) (2015)

Cyclin E1, encoded by the CCNE1 gene, promotes G1/S transition, chromosome instability, and oncogenesis. Here, we show that miR-497 and miR-34a target the 3'-UTR of CCNE1. miR-497 and miR-34a are downregulated in cancer cells and their ectopic expression inhibited cell proliferation and colony formation in vitro, and inhibited tumor growth in a xenograft model. The effect of simultaneous overexpression of miR-497 and miR-34a on the inhibition of cell proliferation, colony formation, and tumor growth, and the downregulation of cyclin E1 was stronger than the effect of each miRNA alone. The synergistic actions of miR-497 and miR-34a partly correlated with cyclin E1 levels. When cells stably expressing CCNE1 were transfected with the Hi-miR-497/34a plasmid, there was no effect on colony formation, compared with that of cells transfected with either Hi-miR497 or Hi-miR34a. These results indicate cyclin E1 is downregulated by both miR-497 and miR-34a, which synergistically retard the growth of human lung cancer cells.
Five years of UK thin surfacing (1997)

Earlier work has reported on the introduction of a thin wearing course and surfacing system UL-M from France, and on the British experience of its use up to that time. This paper comments on the further experience gained since 1993, and classifies the available varieties of other surfacings into thin, ultrathin, and micro surfacing. Thin surfacing has been assessed, using the latest available materials testing and pavement modelling techniques; the test results suggest that 20mm of thin surfacing is equivalent to 20mm of hot rolled asphalt (HRA) wearing course, for pavement design purposes. Formal approval of the use of UL-M on high-speed roads was obtained in January 1995, following extensive testing of its surface characteristics, including surface texture, skid resistance, and noise. Many contracts have now been completed by various companies laying thin surfacing; they include contracts for: overlay to HRA, overlay to porous asphalt, overlay to concrete, housing estate roads, trunk roads, high-speed roads, new construction, and maintenance. During 1996, several local authorities used UL-M for surfacing works during night-time carriageway or lane closures. UL-M thin surfacing has now been approved for use on all classes of roads, and is available throughout the UK. For details of earlier work see IRRD 859798.
Mechanism underlying factor VII deficiency in Jewish populations with the Ala244Val mutation (1999)

We investigated a Sephardic Jewish patient with a mild bleeding diathesis whose plasma levels of factor VII coagulant activity and factor VII antigen were 7% and 9% of normal, respectively. Sequencing demonstrated homozygosity for the Ala244Val mutation and the Arg353Gln polymorphism, which is associated with a modest decrease in factor VII levels. To elucidate the mechanism by which Ala244Val reduced factor VII levels in this patient, transient transfections were performed in COS-1 cells with wild type and mutant factor VII cDNAs and factor VII antigen levels in cell lysates and conditioned media were measured. The secretion of the mutant protein (FVII244V) into the media was 20% of wild type (FVIIwt), and intracellular levels of FVII244V were 60% of FVIIwt. A construct encoding Ala244Val along with the Arg353Gln polymorphism decreased the factor VII level in the media to that observed in the patient's plasma. Pulse-chase experiments demonstrated that FVII244V did not accumulate intracellularly and that low levels of the abnormal protein were maintained throughout the chase. To test the hypothesis that FVII244V results in an unstable molecule, amino acids with smaller (Gly) or larger (Phe) side chains were substituted for Val244 by site-directed mutagenesis. Transient transfection assays with these constructs demonstrated that the side chain of amino acid 244 is crucial in maintaining a proper conformation of the molecule. We conclude that Ala244Val results in a factor VII molecule that is unstable and is probably degraded intracellularly.
Non-Invasive Diagnosis and Prophylaxis in Orthopaedics (1991)

In this paper some ten years of work in bioengineering is described. The central theme is non-invasive diagnosis and prophylaxis. This theme is exemplified in several interrelated sections of work which are described. The work is categorized into: modest beginnings, hip and knee vibration papers, deep venous thrombosis and cavitation in human joints. The philosophy is straightforward--to benefit patients by making harmless measurement.
Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases (2016)

Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases.
Yersinia enterocolitica Septicemia During Long-Term Immunosuppressive Treatment (1984)

Journal Article Yersinia enterocolitica Septicemia During Long-Term Immunosuppressive Treatment Get access Thomas Lenz, Thomas Lenz Department ofMedicine, Klinikum Steglitz, Free University of Berlin, Federal Republic of Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Karl-Ludwig Schulte, Karl-Ludwig Schulte Department ofMedicine, Klinikum Steglitz, Free University of Berlin, Federal Republic of Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Wolfgang Meyer-Sabellek Wolfgang Meyer-Sabellek Department ofMedicine, Klinikum Steglitz, Free University of Berlin, Federal Republic of Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 150, Issue 6, December 1984, Page 963, https://doi.org/10.1093/infdis/150.6.963 Published: 01 December 1984
Deconvolution method for recovering the photon time-of-flight distribution from time-resolved measurements (2012)

A nonparametric deconvolution algorithm for recovering the photon time-of-flight distribution (TOFD) from time-resolved (TR) measurements is described. The algorithm combines wavelet denoising and a two-stage deconvolution method based on generalized singular value decomposition and Tikhonov regularization. The efficacy of the algorithm was tested on simulated and experimental TR data and the results show that it can recover the photon TOFD with high fidelity. Combined with the microscopic Beer-Lambert law, the algorithm enables accurate quantification of absorption changes from arbitrary time-of-flight windows, thereby optimizing the depth sensitivity provided by TR measurements.
CDR3 length in antigen-specific immune receptors. (1994)

In both immunoglobulins (Ig) and T cell receptors (TCR), the rearrangement of V, D, and J region sequence elements during lymphocyte maturation creates an enormous degree of diversity in an area referred to as the complementarity determining region 3 (CDR3) loop. Variations in the particular V, D, and J elements used, precise points of recombination, and random nucleotide addition all lead to extensive length and sequence heterogeneity. CDR3 loops are often critical for antigen binding in Igs and appear to provide the principal peptide binding residues in TCRs. To better understand the physical and selective constraints on these sequences, we have compiled information on CDR3 size variation for Ig H, L (kappa and lambda) and TCR alpha, beta, gamma, and delta. Ig H and TCR delta CDR3s are the most variable in size and are significantly longer than L and gamma chains, respectively. In contrast, TCR alpha and beta chain distributions are highly constrained, with nearly identical average CDR3 lengths, and their length distributions are not altered by thymic selection. Perhaps most significantly, these CDR3 length profiles suggest that gamma/delta TCRs are more similar to Igs than to alpha/beta TCRs in their putative ligand binding region, and thus gamma/delta and alpha/beta T cells may have fundamentally different recognition properties.
Strained Aromatic Oligoamide Macrocycles as New Molecular Clips (2004)

Can one join both ends of a helix? A helical aromatic oligoamide was macrocyclized into a saddle-shaped bifunctional clip molecule that self-assembles into discrete circular dodecamers in the solid state and shows great potential for binding aromatic acid guests in solution. The cyclization step requires that the helix is only partly denatured in the reaction medium.
Rheumatoid arthritis exacerbation caused by exogenous interleukin-12 (2000)

Interleukin-12 (IL-12) is a pleiotropic cytokine with proinflammatory, immunoregulatory, antitumor, and antimetastatic properties. It plays a crucial role in the development of the Th1 response and subsequent interferon-gamma production and enhancement of cell-mediated cytotoxicity. Recently, IL-12 has been used as an experimental therapy for cancer. Given the multiple immunomodulatory properties of IL-12, there are potential concerns associated with its clinical use. Of special interest are the possible side effects of IL-12 therapy in patients with autoimmune diseases, especially those that are T cell mediated, such as rheumatoid arthritis (RA). We present a case of severe RA exacerbation caused by treatment with IL-12 for metastatic cervical cancer. This is the first reported case of RA flare caused by exogenous IL-12.
Role of Protein Kinase C in Regulation of Gene Expression and Relevance to Tumor Promotion (1987)

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) has highly pleiotropic effects on cells in culture and on tissues in vivo, including effects on protein kinase C (PKC) activation and gene expression. In order to determine the mechanism of activation of gene transcription by TPA, DNA sequences whose transcription is modulated in cells undergoing a mitogenic response to TPA were isolated by differential screening of a cDNA library from TPA-treated cells. TPA-S1 corresponds to an mRNA species whose abundance is increased within 1 hr of exposure of quiescent C3H 10T1/2 mouse embryo fibroblasts. TPA-R1 corresponds to an mRNA species whose abundance is decreased in TPA-treated cells. The induction of TPA-S1 is blocked by actinomycin D and is specific for phorbol esters with tumor-promoting activity. The transcription of this sequence is not induced by cycloheximide, nor is there an enhancement of the TPA response. Several lines of evidence demonstrate that PKC activation plays a critical role in the regulation of TPA-S1 expression. The nucleotide and predicted amino acid sequence of TPA-S1 exhibits homology with sequences representing a peptide with erythroid-potentiating activity, a metalloproteinase inhibitor protein, and a murine protein with beta-interferon-like activity. The role of TPA-S1 in tumor promotion is suggested by the expression of this sequence in mouse skin carcinomas induced by dimethyl-benzanthracene-TPA treatment, but not in papillomas or in control tissue. The consideration of signal transduction pathways may be useful in the design of short-term risk assessment assays for agents that act as tumor promoters.
Plasma Ghrelin Levels after Diet-Induced Weight Loss or Gastric Bypass Surgery (2002)

The increase in the plasma ghrelin level with diet-induced weight loss is consistent with the hypothesis that ghrelin has a role in the long-term regulation of body weight. Gastric bypass is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect of the procedure.
Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose (2011)

This article reviews the development of a noninvasive diagnostic for diabetes by detecting ocular glucose. Early diagnosis and daily management are very important to diabetes patients to ensure a healthy life. Commercial blood glucose sensors have been used since the 1970s. Millions of diabetes patients have to prick their finger for a drop of blood 4-5 times a day to check blood glucose levels--almost 1800 times annually. There is a strong need to have a noninvasive device to help patients to manage the disease easily and painlessly. Instead of detecting the glucose in blood, monitoring the glucose level in other body fluids may provide a feasible approach for noninvasive diagnosis and diabetes control. Tear glucose has been studied for several decades. This article reviews studies on ocular glucose and its monitoring methods. Attempts to continuously monitor the concentration of tear glucose by using contact lens-based sensors are discussed as well as our current development of a nanostructured lens-based sensor for diabetes. This disposable biosensor for the detection of tear glucose may provide an alternative method to help patients manage the disease conveniently.
Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer. (2003)

Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aberrant DNA methylation is associated with low dietary folate intake, which is aggravated by high alcohol intake. The relationship between promoter methylation of genes involved in CRC carcinogenesis and folate and alcohol intake was investigated. Methylation of the APC-1A, p14(ARF), p16(INK4A), hMLH1, O(6)-MGMT, and RASSF1A promoters was studied using methylation-specific PCR in 122 sporadic CRCs, derived from patients with folate and alcohol intake at either the lower or the higher quintiles of the distribution. Overall, promoter hypermethylation frequencies observed were: 39% for APC; 33% for p14(ARF); 31% for p16(INK4A); 29% for hMLH1; 41% for O(6)-MGMT; and 20% for RASSF1A. For each of the tested genes, the prevalence of promoter hypermethylation was higher in CRCs derived from patients with low folate/high alcohol intake (n = 61) when compared with CRCs from patients with high folate/low alcohol intake (n = 61), but the differences were not statistically significant. The number of CRCs with at least one gene methylated was higher (84%) in the low folate intake/high alcohol intake group when compared with the high folate intake/low alcohol intake group (70%; P = 0.085). Despite the size limitations of this study, these data suggest that folate and alcohol intake may be associated with changes in promoter hypermethylation in CRC.
Use of cardiac troponin I to diagnose perioperative myocardial infarction in coronary artery bypass grafting (1994)

Cardiac troponin I (cTnI) is a regulatory protein unique to myocardium. We used a cardiospecific 30-min ELISA to measure cTnI in EDTA-plasma samples serially drawn from 28 patients before and after coronary artery bypass grafting (CABG)--26 elective and 2 salvage cases. The cTnI increase in 22 of the elective CABG patients, who did not have perioperative myocardial infarction (not-PMI), reflected the inevitable myocardial damage caused by cannulation and cardioplegic arrest, with peak values of 1.7 +/- 1.0 microgram/L (mean + 2 SD = 3.7 micrograms/L), the peaks occurring on average 8 h (range 4-24) after aortic unclamping. Two of the 22 not-PMI, elective CABG patients showed cTnI peaks > 3.0 micrograms/L (3.9 and 3.4 micrograms/L), indicating more extensive perioperative myocardial damage than the other 20, as confirmed by clinical and electrocardiographic or echocardiographic signs, although creatine kinase isoenzyme MB (CKMB) activity was below our PMI decision limit of 20 U/L (25 degrees C). As classified by electrocardiography, echocardiography, and increased CKMB activity, four of the 26 elective CABG patients did have a PMI. One patient with Q-wave PMI had peak cTnI approximately 30 micrograms/L, and three with non-Q-wave PMI had lower peak values (approximately 5 micrograms/L). The two salvage CABG cases had increased cTnI before surgery. One developed a Q-wave acute myocardial infarction with a 3-h cTnI peak of approximately 35 micrograms/L. We conclude that, after elective CABG, cTnI peaks > 3.7 micrograms/L and concentrations > 3.1 micrograms/L at 12 h or 2.5 micrograms/L at 24 h indicate PMI with high probability.
PSORIATIC ARTHRITIS: OUTCOME OF DISEASE SUBSETS AND RELATIONSHIP OF JOINT DISEASE TO NAIL AND SKIN DISEASE (1994)

Subgroups of PsA have been described but their relationship to the mode of onset of arthritis, to DIP joint disease and to nail and skin disease remains controversial. Therefore, the pattern of disease was documented in 100 patients with PsA in whom the mode of onset was known. The patients were divided into six subgroups: monoarthritis; DIP joint disease only; oligoarthritis; polyarthritis; spondyloarthropathy and arthritis mutilans. Sixty-four patients changed pattern. Nail disease (67% of total) was more common in patients with DIP joint disease (27% of total) and was significantly associated with adjacent DIP joint disease. Skin and nail disease severity did not correlate with joint severity, joint activity or functional status, nor differ between subgroups. Therefore, the mode of onset does not predict outcome in the majority. The topographic association of nail disease and involvement of the adjacent DIP joints suggests a common local inflammatory mechanism.
The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target (2009)

Expression of Axl tyrosine kinase in pancreatic cancers confers an adverse prognostic influence, and represents a new therapeutic target in this malignancy.
Site-specific mutations in the mature form of human IL-18 with enhanced biological activity and decreased neutralization by IL-18 binding protein (2001)

IL-18 can be considered a proinflammatory cytokine mediating disease as well as an immunostimulatory cytokine that is important for host defense against infection and cancer. The high-affinity, constitutively expressed, and circulating IL-18 binding protein (IL-18BP), which competes with cell surface receptors for IL-18 and neutralizes IL-18 activity, may act as a natural antiinflammatory as well as immunosuppressive molecule. In the present studies, the IL-18 precursor caspase-1 cleavage site was changed to a factor Xa site, and, after expression in Escherichia coli, mature IL-18 was generated by factor Xa cleavage. Mature IL-18 generated by factor Xa cleavage was fully active. Single point mutations in the mature IL-18 peptide were made, and the biological activities of the wild-type (WT) IL-18 were compared with those of the mutants. Mutants E42A and K89A exhibited 2-fold increased activity compared with WT IL-18. A double mutant, E42A plus K89A, exhibited 4-fold greater activity. Unexpectedly, IL-18BP failed to neutralize the double mutant E42A plus K89A compared with WT IL-18. The K89A mutant was intermediate in being neutralized by IL-18BP, whereas neutralization of the E42A mutant was comparable to that in the WT IL-18. The identification of E42 and K89 in the mature IL-18 peptide is consistent with previous modeling studies of IL-18 binding to IL-18BP and explains the unusually high affinity of IL-18BP for IL-18.