gebhart/patrepeval huggingface dataset:
Th2 and Tc2 Cells in the Regulation of GVHD, GVL, and Graft Rejection: Considerations for the Allogeneic Transplantation Therapy of Leukemia and Lymphoma (2000)

Allogeneic stem cell transplantation (SCT) represents a curative treatment option for patients with leukemia and lymphoma. T lymphocytes contained in the allograft mediate a graft-versus-leukemia (GVL) effect and prevent graft rejection; however, T cells also initiate graft-versus-host disease (GVHD). Identification of T cell populations which mediate a GVL effect and prevent rejection with reduced GVHD will likely improve transplantation outcome. T cells exist in four functionally-defined populations, the CD4+, Th1/Th2 and CD8+, Tc1/Tc2 subsets. Th1-type CD4 cells primarily secrete type I cytokines (IL-2 and IFN-gamma), whereas Th2 cells secrete type II cytokines (IL-4, IL-5, and IL-10). Similarly, the CD8+ Tc1 and Tc2 cells differentially secrete the type I and type II cytokines, respectively. In addition to cytokine secretion, Tc1 and Tc2 populations mediate cytolytic effects, with Tc1 cells utilizing both perforin- and fas-based killing pathways, whereas Tc2 cells primarily utilize perforin-mediated cytolysis. In murine transplantation models of graft rejection, GVHD, and GVL effects, we have evaluated such functional T cell subsets for their ability to differentially mediate and regulate transplantation responses. These studies demonstrate that donor Th2 cells do not initiate acute GVHD, and can regulate the GVHD mediated by unmanipulated donor T cells without impairing alloengraftment. Additional experiments have shown that allospecific donor Tc2 cells result in reduced GVHD, and mediate a significant GVL effect. Thirdly, we have demonstrated that non-host reactive Tc2 cells with veto-like activity can potently abrogate marrow rejection independent of GVHD. Together, these results demonstrate that functionally-defined donor Th2 and Tc2 populations play an important role in the regulation of GVHD, the prevention of graft rejection, and the mediation of GVL effects, and suggest that utilization of Th2 and Tc2 cells in clinical allogeneic SCT may have potential for improving treatment outcome.
Kinetic and mechanical parameters of pure and cryoprecipitate fibrin (1993)

The kinetics of formation (clot time; CT) as well as a mechanical parameter (breaking strength; BS) of fibrin were measured at various concentrations of fibrinogen. In a pure system and for a fixed level of thrombin, the CT-fibrinogen dependency was biphasic, reaching a minimum in the range 1-8 μM fibrinogen. A new parameter, [Fib]min, the minimal fibrinogen concentration required for phase change, was derived from this. The [Fib]min values of pure fibrinogen activated with thrombin, ranged between 0.15 and 0.25 μM fibrinogen. Single donor cryoprecipitate (cryo) had similar kinetics and [Fib]min value. A technique for measuring the innate breaking strength of fibrin, independently of its adhesive properties, is described. For pure fibrin activated with thrombin, the BS was a linear function of fibrinogen concentration, with numeric values for the slope of 0.84 g/μM and slopec, (with 2.5 mM Ca) of 2.26 g/μM, which transformed into a general description of the BS of fibrin and the fibrinogen level according to the equation: BS = μ [Fib]. The constants μ = 18.9 dyne/μM-cm2 and μc = 55.7 dyne/μM-cm2 reflect the innate strength of fibrin clot per cross-section area. Cryo fibrin exhibited a BS equivalent to its fibrinogen level in a pure system. Although scanning electron microscopy of pure and cryo fibrin formed at equivalent fibrinogen levels revealed significant ultrastructural disparity between the pure and cryo fibrin, the kinetics of formation and the mechanical parameters of both were comparable.
Sulfonation and Sialylation of Gonadotropins in Women during the Menstrual Cycle, after Menopause, and with Polycystic Ovarian Syndrome and in Men (2007)

The observed variations in sialic acid and sulfonated residues on serum gonadotropins are suggested to reflect alterations in the isoform composition of the hormones secreted by the pituitary, resulting in modulations of their biological properties, such as half-life in blood.
Clostridium difficile Toxin A Stimulates Macrophage- Inflammatory Protein-2 Production in Rat Intestinal Epithelial Cells (1998)

Neutrophil infiltration of the colonic mucosa is a hallmark of Clostridium difficile toxin A-mediated enterocolitis. Macrophage-inflammatory protein-2 (MIP-2) is a potent neutrophil chemoattractant secreted by rat macrophages and epithelial cells in response to inflammatory stimuli. In this work, we report that administration of toxin A into rat ileal loops increased mucosal levels of MIP-2 before the onset of fluid secretion and mucosal neutrophil infiltration. Administration of rabbit anti-MIP-2 IgG, but not control IgG, reduced toxin A-mediated secretion (by 58%), mucosal permeability (by 80%), and myeloperoxidase activity (by 85%). Immunohistochemical analysis demonstrated increased MIP-2 expression in intestinal epithelial and lamina propria cells 1 h after toxin A administration. Intestinal epithelial cells purified from toxin A-exposed ileal loops also showed increased MIP-2 mRNA expression and MIP-2 protein release that was inhibited by pretreatment of rats with the transcriptional inhibitor actinomycin D. These results indicate that C. difficile toxin A induces MIP-2 release from intestinal epithelial cells and that MIP-2 contributes to neutrophil mucosal influx during toxin A enteritis.
Role of Reactive Oxygen Species and p53 in Chromium(VI)-induced Apoptosis (1999)

Apoptosis is a programmed cell death mechanism to control cell number in tissues and to eliminate individual cells that may lead to disease states. The present study investigates chromium(VI) (Cr(VI))-induced apoptosis and the role of reactive oxygen species (ROS) and p53 in this response. Treatment of human lung epithelial cells (A549) with Cr(VI) caused apoptosis as measured by DNA fragmentation, mitochondria damage, and cell morphology. Cr(VI)-induced apoptosis is contributed to ROS generation, resulting from cellular reduction of Cr(VI) as measured by flow cytometric analysis of the stained cells, oxygen consumption, and electron spin resonance spin trapping. Scavengers of ROS, such as catalase, aspirin, and N-acetyl-L-cysteine, decreased Cr(VI)-induced apoptosis, whereas NADPH and glutathione reductase, enhancers of Cr(VI)-induced ROS generation, increased it. p53 is activated by Cr(VI), mostly by ROS-mediated free radical reactions. Cr(VI)-induced ROS generation occurred within a few minutes after Cr(VI) treatment of the cells, whereas p53 induction took at least 5 h. The level of Cr(VI)-induced apoptosis was similar in both p53-positive cells and p53-negative cells independent of p53 status in the early stage (0-3 h) of Cr(VI) treatment. However, at the later stage (3-24 h), the level of the apoptosis is higher in p53-positive cells than in p53-negative cells. These results suggest that ROS generated through Cr(VI) reduction is responsible to the early stage of apoptosis, whereas p53 contributes to the late stage of apoptosis and is responsible for the enhancement of Cr(VI)-induced apoptosis at this stage.
Targeting TACE-dependent EGFR ligand shedding in breast cancer (2007)

The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop that provides an oncogenic stimulus in the absence of proto-oncogene mutation. Targeting this protease, TNF-alpha-converting enzyme (TACE; also referred to as a disintegrin and metalloproteinase 17 [ADAM17]), with small molecular inhibitors or siRNAs reverted the malignant phenotype in a breast cancer cell line by preventing mobilization of 2 crucial growth factors, TGF-alpha and amphiregulin. We show that TACE-dependent ligand shedding was prevalent in a series of additional breast cancer cell lines and, in all cases examined, was amenable to inhibition. Using existing patient outcome data, we demonstrated a strong correlation between TACE and TGFA expression in human breast cancers that was predictive of poor prognosis. Tumors resulting from inappropriate activation of the EGFR were common in multiple tissues and were, for the most part, refractory to current targeted therapies. The data presented here delineate the molecular mechanism by which constitutive EGFR activity may be achieved in tumor progression without mutation of the EGFR itself or downstream pathway components and suggest that this important oncogenic pathway might usefully be targeted upstream of the receptor.
Idiopathic CD4 lymphocytopenia (2006)

The manifestation of opportunistic infections calls for the evaluation of the immune system for CD4 lymphocytopenia. The differential diagnosis of this condition in adults comprises primarily HIV infection and less often other diseases or drugs. Idiopathic CD4 lymphocytopenia is very rare. The clinical significance of low CD4 cell counts in HIV negative patients still awaits its systematic analysis. Prophylaxis of opportunistic infections is oriented at the recommendations of HIV-infected individuals and causal treatment remains experimental.
Association Between Adherence to Diuretic Therapy and Health Care Utilization in Patients with Heart Failure (2003)

Patients taking a greater proportion of diuretic agents on schedule may decrease the risk of cardiovascular- and heart failure-related hospitalizations. If these findings are confirmed by a larger study, interventions to improve adherence and patient health outcomes should consider the timing of doses as well as the number of daily doses of a diuretic.
Sialyl Tn‐expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells (2014)

Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how they contribute to the tilt immune response remains poorly defined. In this study, we sought to evaluate the impact of the malignant phenotype-associated glycan, sialyl-Tn (STn) in the function of the key orchestrators of the immune response, the dendritic cells (DCs). In high grade bladder cancer tissue, the STn antigen is significantly overexpressed and correlated with the increased expression of ST6GALNAC1 sialyltransferase. Bladder cancer tissue presenting elevated expression of ST6GALNAC1 showed a correlation with increased expression of CD1a, a marker for bladder immature DCs and showed concomitant low levels of Th1-inducing cytokines IL-12 and TNF-α. In vitro, human DCs co-incubated with STn(+) bladder cancer cells, had an immature phenotype (MHC-II(low), CD80(low) and CD86(low)) and were unresponsive to further maturation stimuli. When contacting with STn(+) cancer cells, DCs expressed significantly less IL-12 and TNF-α. Consistent with a tolerogenic DC profile, T cells that were primed by DCs pulsed with antigens derived from STn(+) cancer cells were not activated and showed a FoxP3(high) IFN-γ(low) phenotype. Blockade of STn antigens and of STn(+) glycoprotein, CD44 and MUC1, in STn(+) cancer cells was able to lower the induction of tolerance and DCs become more mature. Overall, our data suggest that STn-expressing cancer cells impair DC maturation and endow DCs with a tolerogenic function, limiting their capacity to trigger protective anti-tumour T cell responses. STn antigens and, in particular, STn(+) glycoproteins are potential targets for circumventing tumour-induced tolerogenic mechanisms.
High-speed multispectral fluorescence lifetime imaging implementation for in vivo applications (2010)

Fluorescence lifetime imaging microscopy (FLIM) offers a noninvasive approach for characterizing the biochemical composition of biological tissue. In recent years, there has been an increasing interest in the application of multispectral FLIM for medical diagnosis. Central to the clinical translation of FLIM technology is the development of robust, fast, and cost-effective FLIM instrumentation suitable for in vivo tissue imaging. Unfortunately, the predominant multispectral FLIM approaches suffer from limitations that impede the development of high-speed instruments for in vivo applications. We present a cost-effective scanning multispectral FLIM implementation capable of achieving pixel rates on the order of tens of kilohertz, which will facilitate the evaluation of FLIM for in vivo applications.
Attitudes towards implementation of surveillance‐based parasite control on K entucky T horoughbred farms – Current strategies, awareness and willingness‐to‐pay (2014)

Traditional approaches for equine parasite control are still widely used in the Kentucky Thoroughbred industry. The data suggest that respondents were only willing to make these changes if they could be given assurance that the surveillance-based approach would prevent anthelmintic resistance and decrease health risks significantly for the horses.
Antitumor activity of creatine analogs produced by alterations in pancreatic hormones and glucose metabolism. (1998)

When rats bearing the 13,762 mammary carcinoma were treated with intravenously administered creatine analogs, cyclocreatine, beta-guanidinopropionic acid or creatine phosphate on days 4 through 8 and 14 through 18 post tumor implantation, the tumor growth delay produced varied with whether the animals were drinking water or sugar water over the course of the study. The tumor growth delays increased when the animals drank sugar water from 9.3, 1.6 and 7.6 days for cyclocreatine, beta-guanidinopropionic acid and creatine phosphate, respectively, to 15.0, 6.3 and 12.6 days. Blood glucose was decreased over the course of the creatine analog treatment regimen and the skeletal muscle transport protein GLUT-4 increased 1.5 to 2-fold with the creatine analog treatments. Plasma insulin was profoundly decreased to 20-25% of normal by the creatine analog treatment while plasma glucagon levels were increased. Plasma somatostatin increased 3- to 4-fold during the administration of the creatine analogs. These results implicate alterations in pancreatic hormone balance in the antitumor activity of these creatine analogs.
Pulsed laser welding parameters (2002)

Laser welding provides improved healing along with greater ease and speed compared with suture tissue joining. Because of the photothermal mechanism, a certain amount of heat damage accompanies laser welding. Because of the CW, hand-held delivery to a visually determined end-point, the margin between a weak, underexposed weld and a large zone of tissue destruction is narrow (i.e. narrow therapeutic index). This CW exposure produces unwanted collateral thermal injury even in the case where the weld site itself is exposed ideally. We studied a series of pulsed laser parameters in welding a rat skin model in vitro to determine 1) if comparable weld strength could be obtained to CW welding parameters; 2) if thermal injury could, in fact, be spatially confined and 3) what the appropriate pulse width and interval is to achieve this goal.
The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity (2011)

Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r(2) = 0.399, P = 0.001) and PDP1 protein expression (r(2) = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α (r(2) = 0.310, P = 0.002) and PDK2 protein (r(2) = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼ 18% of the variance in PDP activity (r(2) = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼ 38% of the variance in PDP activity (r(2) = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity).
Interleukin-2 induces peroxide production by primed normodense eosinophils of patients with asthma. (2003)

In this study we assessed, by flow cytometry, the effect of interleukin 2 (IL-2) on the oxidative burst of normodense eosinophils (Eos's) isolated from 15 patients with moderately severe extrinsic asthma and 17 controls. We found that IL-2 significantly induced peroxide (H2O2) production in normodense Eos's from patients with asthma on a time kinetics study. This rise was higher in patients with immunoglobulin E levels > 180 IU/mL versus normal immunoglobulin E values. The effect of IL-2 was partially blocked by using anti-Tac antibody. In contrast, IL-2 decreased H2O2 production in normodense Eos's from controls. Cell surface expression of CD25, CD122, CD132, and CD69 were also determined and no statistical differences were found between both groups. In conclusion, IL-2 is able to increase H2O2 production by normodense Eos's isolated from patients with asthma and it may contribute to bronchial epithelium damage and chronic inflammation.
Brain anatomy of major depression II. Focus on amygdala (2011)

Here, we briefly summarize the most consistent structural magnetic resonance imaging (MRI) studies on amygdala in major depression and debate the effects of clinical variables on amygdalar morphology.
Cell Surface Nucleolin as a Target for Anti-Cancer Therapies (2014)

A large number of mostly recent reports show enhanced expression of the multi-functional protein nucleolin (NCL) on the surface of activated lymphocytes, angiogenic endothelial and many different types of cancer cells. Translocation of NCL at the external side of the plasma membrane occurs via a secretory pathway independent of the endoplasmic reticulum-Golgi complex, requires intracellular intact actin cytoskeleton, and seems to be mediated by a variety of factors. Cell surface NCL serves as a binding partner of several molecules implicated in cell differentiation, adhesion, and leukocyte trafficking, inflammation, angiogenesis and tumor development, mediating their biological activities and in some cases, leading to their internalization. Accumulating evidence validates cell surface NCL as a strategic target for treatment of cancer, while its property of tumor-specific uptake of targeted ligands seems to be useful for the development of non-invasive imaging tools for the diagnosis of cancer and for the targeted release of chemotherapeutic drugs. The observation that cell surface NCL exists in complexes with several other proteins implicated in tumorigenesis and angiogenesis suggests that targeting cell surface NCL might trigger multi-inhibitory effects, depending on the cell type. This review summarizes papers and patents related to the redistribution and the biological functions of cell surface NCL, with emphasis on the potential importance and advantages of developing efficient anti-cell surface NCL strategies.
Evidence that enzymes of a novel aerobic 2‐amino‐benzoate metabolism in denitrifying Pseudomonas are coded on a small plasmid (1990)

A new pathway for aerobic metabolism of 2-aminobenzoate which proceeds via anthranoyl-CoA has recently been revealed in a Pseudomonas strain KB740. This bacterial strain was found to contain a small 8.1-kbp plasmid pKB740 which appears to harbour the genes encoding for two key enzymes catalyzing the initial reactions of the pathway, 2-aminobenzoate coenzyme A ligase and 2-aminobenzoyl-coenzyme A monooxygenase/reductase. The evidence is as follows: The plasmid content of the culture varied by a factor of ten depending on the growth substrates; it was highest when cells were grown aerobically on 2-aminobenzoate. The plasmid pKB740 could be introduced into Escherichia coli strain JM83 by transformation. Wild-type E. coli and E. coli JM83 are unable to metabolize 2-aminobenzoate whereas the transformed E. coli JM83 cells could grow with this aromatic compound as sole organic substrate and oxidize it completely to CO2. The plasmid recovered from E. coli had the same restriction map as the original plasmid, but was dimerized. The two key enzyme activities were demonstrated in the transformed E. coli in sufficiently high amounts to explain growth. They appear to be regulated on the transcription level by induction; they were formed only during aerobic growth in the presence of 2-aminobenzoate, as in the parent Pseudomonas. The N-terminal amino acid sequence of 2-aminobenzoyl-CoA monooxygenase/reductase was similar to the consensus sequence of the FAD binding site of different flavoenzymes. The data also prove that the enzyme with two flavin functions is a alpha 2 homodimer. Southern blotting of digested chromosomal and plasmid DNA and hybridization against a labelled 15-base oligonucleotide derived from the N-terminal amino acid sequence of 2-aminobenzoyl-CoA monooxygenase/reductase revealed that the gene for this enzyme is coded on the plasmid rather than on the chromosome. The gene was localized on a 3.2-kbp restriction fragment. The formation of 2-aminobenzoyl-CoA monooxygenase/reductase protein in transformed E. coli was demonstrated by Western blotting of proteins of cell extracts separated by SDS/PAGE. The enzyme protein band, which was stained by a procedure based on antibodies against 2-aminobenzoyl-CoA monooxygenase/reductase, was demonstrated in transformed E. coli.
Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligodeoxynucleotides (1999)

Heparanase activity correlates with the metastatic potential of tumor cells. Moreover, the anti-metastatic effect of non-anti-coagulant species of heparin and certain sulfated polysaccharides was attributed to their heparanase-inhibiting activity. We investigated the effect of a chemically sulfated polysaccharide (laminarin), consisting primarily of beta-1,3 glucan (sodium laminarin), and of synthetic phosphorothioate oligodeoxynucleotides, primarily phosphorothioate homopolymer of cytidine (SdC28), on heparanase activity and tumor metastasis. Investigation of the ability of tumor cells to degrade heparan sulfate in intact extracellular matrix revealed that heparanase activity expressed by B16-BL6 mouse melanoma cells and 13762 MAT rat mammary adenocarcinoma cells was effectively inhibited by LS (50% inhibition at 0.2-1 microgram/ml), but there was no inhibition by sodium laminarin up to a concentration of 50 microgram/ml. Complete inhibition of the melanoma heparanase was obtained in the presence of 0.1 microM SdC28. A single i.p. injection of laminarin sulfate, but not of sodium laminarin, before i.v. inoculation of the melanoma or breast-carcinoma cells inhibited the extent of lung colonization by the tumor cells by 80 to 90%. Similar inhibition was exerted by 0.1 microM SdC28. At the effective concentrations, both compounds had a small effect on proliferation of the tumor cells and on growth of the primary tumors in vivo. These results further emphasize the involvement of heparanase in tumor metastasis and the potential clinical application of diverse heparanase-inhibiting molecules such as sulfated polysaccharides and synthetic polyanionic molecules.