gebhart/patrepeval huggingface dataset:
Porcine Adenoviruses: An Update on Genome Analysis and Vector Development (2000)

Although porcine adenoviruses (PAdV) are present in the swine populations worldwide, they usually do not cause any disease, or the infection is only manifested in a mild diarrhoea or respiratory signs. The importance of adenoviruses, however, is constantly growing as there is a possibility of developing them into viral vector vaccines against more significant swine pathogens. A short summary of the well-established facts of porcine adenoviruses is given and recent developments of the genetic analysis of these viruses are discussed in detail. The possibilities of vector development and examples of vector vaccines already reported in the literature are mentioned.
Micromachining and Microgenetics: What Are They and Where Do They Work Together? (1996)

PCR provides specific amplification of very small quantities of DNA by employing DNA polymerase extension under tightly-controlled temperature cycling. The reactions are typically performed in IO's to lOO's of microliters in plastic tubes. The role of silicon-based processing in improving upon the PCR process (cost and performance) by reducing sample requirements, increasing throughput, and improving temperature cycling uniformity and ramping rates are contrasted with issues regarding surface chemistry and user interfaces at small scales. A platform for preparing test arrays and cycling of multiple sites with direct monitoring of temperature AND reaction progress is demonstrated in both silicon and molded, plastic parts. The relevance to genetic screening is addressed.
Poster 10 Is There a Chondroprotective Effect of Autologous Platelet Integrated Concentrate (APIC) on an Osteoarthritis (OA) Rabbit Model? A Pilot Study (2012)

J. M. Cuellar, Stock options or bond holdings: Cytonics Corp, Nevro Corp. To test the hypotheses that intra-articular administration of APIC in a rabbit model of post-traumatic arthritis will attenuate progression of cartilage damage and modulate cytokine response in the synovial fluid. New Zealand White rabbits underwent blood draw that was immediately processed to produce APIC. Transection of the anterior cruciate ligament (ACL) was performed to initiate the development of OA. The rabbits were divided into two groups. The treatment group (N=12) was administered 3 doses of APIC at 1, 4 and 14 days post-surgery. This group was monitored for 6 weeks (N=6) or 12 weeks (N=6). The control group received no treatment post-surgery. All rabbits underwent synovial fluid sampling at various time points. Rabbit OA model, ACL injury. 18 rabbits. Injection of APIC. Cartilage pathology was evaluated by macroscopic examination and histological evaluation of the femoral and tibial using the OARSI grading scale. Synovial fluid from each group was analyzed for known biomarkers of OA. Macroscopic and histologic evaluation of the femoral and tibia demonstrated less degeneration in the treatment group compared to the control group. This pilot study suggests that injection of APIC at the time of intra-articular injury may prevent cytokine action from initiating the degradative cascade that leads to OA in an animal model protecting from cartilage loss following injury. This activity may be explained by the 5-10 fold increased concentration of alpha-2-macroglobulin (A2M) in APIC over its concentration in blood. This conclusion is in agreement with our in-vitro and ex-vivo experiments that demonstrate the chondroprotective effect of A2M on cartilage. The cartilage protective effects of APIC and A2M will be confirmed in human clinical trials.
Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis (2005)

Resolvin E1 (RvE1; 5S,12R,18R-trihydroxyeicosapentaenoic acid) is an antiinflammatory lipid mediator derived from omega-3 fatty acid eicosapentaenoic acid (EPA). At the local site of inflammation, aspirin treatment enhances EPA conversion to 18R-oxygenated products, including RvE1, which carry potent antiinflammatory signals. Here, we obtained evidence for reduced leukocyte infiltration in a mouse peritonitis model, where the administration of EPA and aspirin initiated the generation of RvE1 in the exudates. Similar results were obtained with the administration of synthetic RvE1, which blocked leukocyte infiltration. RvE1 also protected against the development of 2,4,6-trinitrobenzene sulfonic acid-induced colitis. The beneficial effect was reflected by increased survival rates, sustained body weight, improvement of histologic scores, reduced serum anti-2,4,6-trinitrobenzene sulfonic acid IgG, decreased leukocyte infiltration, and proinflammatory gene expression, including IL-12 p40, TNF-alpha, and inducible nitric oxide synthase. Thus, the endogenous lipid mediator RvE1 counter-regulates leukocyte-mediated tissue injury and proinflammatory gene expression. These findings show an endogenous mechanism that may underlie the beneficial actions of omega-3 EPA and provide targeted approaches for the treatment of intestinal inflammation.
Implantation of Schwann cells in rat tendon autografts as a model for peripheral nerve repair: Long term effects on functional recovery (2008)

Cultured Schwann cells in tendon autografts for nerve repair improve the early phase of nerve regeneration in rat sciatic nerves as judged by the rate of axonal outgrowth. We tested the long-term effects on functional recovery using measurements of muscle force, the number of axons and myelination, using morphometry. In addition, we recorded wet weight of the gastrocnemius muscle. Schwann cell cultures were prepared from predegenerated nerves. Ten and 15 mm defects in rat sciatic nerves were bridged using bilateral tendon autografts with Schwann cell-seeded tendon autografts on one side, and untreated tendon autografts on the other. Animals were evaluated at six and 12 weeks, respectively. At six weeks, myelination, as judged by G-ratio (ratio of axonal diameter to diameter of nerve fibres), was significantly increased in tendon autografts pretreated with Schwann cells in 10mm defects. No such difference was seen in the 15 mm defects. We found no difference in functional recovery, other morphometric variables, or muscle weight between the two grafts. We conclude that early effects on nerve regeneration using transplantation of cultured Schwann cells in rat sciatic nerves are temporary. Other strategies are necessary to obtain lasting effects on functional recovery.
Intravitreal Devices for the Treatment of Vitreous Inflammation (2012)

The eye is a well-suited organ for local delivery of therapeutics to treat vitreous inflammation as well as other pathologic conditions that induce visual loss. Several conditions are particularly challenging to treat and often require chronic courses of therapy. The use of implantable intravitreal devices for drug delivery is an emerging field in the treatment of vitreous inflammation as well as other ophthalmologic diseases. There are unique challenges in the design of these devices which include implants, polymers, and micro- and nanoparticles. This paper reviews current and investigational drug delivery systems for treating vitreous inflammation as well as other pathologic conditions that induce visual loss. The use of nonbiodegradable devices such as polyvinyl alcohol-ethylene vinyl acetate polymers and polysulfone capillary fibers, and biodegradable devices such as polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid, polycaprolactones, and polyanhydrides are reviewed. Clinically used implantable devices for therapeutic agents including ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and dexamethasone are described. Finally, recently developed investigational particulate drug delivery systems in the form of liposomes, microspheres, and nanoparticles are examined.
Role of the translationally controlled tumor protein in DNA damage sensing and repair (2012)

The translationally controlled tumor protein (TCTP) is essential for survival by mechanisms that as yet are incompletely defined. Here we describe an important role of TCTP in response to DNA damage. Upon exposure of normal human cells to low-dose γ rays, the TCTP protein level was greatly increased, with a significant enrichment in nuclei. TCTP up-regulation occurred in a manner dependent on ataxia-telangiectasia mutated (ATM) kinase and the DNA-dependent protein kinase and was associated with protective effects against DNA damage. In chromatin of irradiated cells, coimmunoprecipitation experiments showed that TCTP forms a complex with ATM and γH2A.X, in agreement with its distinct localization with the foci of the DNA damage-marker proteins γH2A.X, 53BP1, and P-ATM. In cells lacking TCTP, repair of chromosomal damage induced by γ rays was compromised significantly. TCTP also was shown to interact with p53 and the DNA-binding subunits, Ku70 and Ku80, of DNA-dependent protein kinase. TCTP knockdown led to decreased levels of Ku70 and Ku80 in nuclei of irradiated cells and attenuated their DNA-binding activity. It also attenuated the radiation-induced G(1) delay but prolonged the G(2) delay. TCTP therefore may play a critical role in maintaining genomic integrity in response to DNA-damaging agents.
The Use of Thymidylate Synthase Inhibitors in the Treatment of Advanced Colorectal Cancer: Current Status (1999)

Abstract The combination of 5-fluorouracil (5-FU) and leucovorin has been the unofficial “standard” therapy for patients with colorectal cancer for over a decade. Recently, however, a number of new agents targeted against the enzyme thymidylate synthase have been synthesized and are in various stages of development. The currently available thymidylate synthase inhibitors are discussed. Enormous efforts have been made over the years to improve the efficacy of 5-FU, the most popular of these agents. Biochemical modulation by leucovorin has been the most successful so far. Continuous infusion schedules also appear to be advantageous over bolus administration. However, marked intra- and interpatient variability, combined with nonlinear elimination kinetics and erratic oral bioavailability are relative limitations to further development of 5-FU. New oral 5-FU prodrugs such as UFT, S-1, and Capecitabine may help to overcome some of these difficulties. Eniluracil, a potent inhibitor of the enzyme dihydropyrimidine dehydrogenase, may also help by overcoming potential 5- FU resistance mechanisms, in addition to increasing its bioavailability. Of the antifolate-based inhibitors, Tomudex is in the most advanced stage of development. Similar efficacy with 5-FU and a convenient schedule may suggest a role in future combination regimens. It is quite likely that even the most optimal thymidylate synthase inhibition will have limitations in terms of clinical efficacy. Novel combinations of 5-FU or its analogs with agents that have different mechanisms of action (e.g., oxaliplatin, irinotecan) could provide important new opportunities for improving the outlook of patients with colorectal cancer.
Sur la science en France, 1860-1940. A propos de deux ouvrages récents de Mary Jo Nye et Harry W. Paul (1988)

Pestre Dominique. Sur la science en France, 1860-1940. A propos de deux ouvrages récents de Mary Jo Nye et Harry W. Paul. In: Revue d'histoire des sciences, tome 41, n°1, 1988. pp. 75-83.
High-affinity-receptor-mediated uptake and degradation of glucose-modified proteins: a potential mechanism for the removal of senescent macromolecules. (1985)

Proteins that have been modified by long-term exposure to glucose accumulate advanced glycosylation end products (AGE) as a function of protein age. In these studies, we have characterized the interaction of AGE-protein with mouse peritoneal macrophages, using AGE-modified bovine serum albumin (AGE-BSA, prepared by incubation with glucose) as a probe. AGE-BSA was specifically bound to cells at 4 degrees C and was taken up and degraded at 37 degrees C; these processes were concentration dependent and saturable. Competition experiments with AGE-BSA, BSA incubated with phosphate-buffered saline rather than glucose, and yeast mannan demonstrated that macrophages specifically recognize AGE on proteins by a receptor that is completely distinct from the mannose/fucose receptor. Scatchard analysis of AGE-BSA binding data indicated that there are approximately 1.06 X 10(5) receptors per macrophage, with an affinity constant of 1.75 X 10(-11) M. Specific binding of AGE-BSA to the macrophage receptor was competitively inhibited by BSA that had been chemically coupled to a synthetic analogue of the specific AGE, 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI-BSA). FFI-BSA was also taken up by macrophages in a concentration-dependent, saturable manner. Prior incubation of macrophages with AGE-BSA failed to influence the subsequent uptake and degradation of added AGE-BSA. Thus, the AGE receptor does not appear to be down-regulated by exposure to AGE-proteins. Results from these studies suggest that AGE could act in vivo as a specific signal for recognition and degradation of senescent macromolecules. Incomplete removal of AGE-proteins by macrophages may ultimately give rise to some of the physiologic changes that occur with normal aging.
Anxious depression and early changes in the HAMD-17 anxiety-somatization factor items and antidepressant treatment outcome (2010)

The objective of this study was to assess the relationship between early changes in anxiety/somatization symptoms and treatment outcome among major depressive disorder patients during a 12-week trial of fluoxetine. We also examined the relationship between anxious depression and treatment response. Five hundred and ten major depressive disorder patients received 12 weeks of fluoxetine with flexible dosing [target dosages: 10 mg/day (week 1), 20 mg/day (weeks 2-4), 40 mg/day (weeks 4-8), and 60 mg/day (weeks 5-12)]. We assessed the relationship between early changes in 17-item Hamilton Rating Scale for Depression (HAMD-17)-anxiety/somatization factor items and depressive remission, as well as whether anxious depression at baseline predicted remission at study endpoint. Baseline HAMD-17 scores were considered as covariates and the Bonferroni correction (P < or = 0.008) was used for multiple comparisons. Adjusting for baseline HAMD-17 scores, patients who experienced greater early improvement in somatic symptoms (gastrointestinal) were significantly more likely to attain remission (HAMD-17 <8) at endpoint than those without early improvement (P=0.006). Early changes in the remaining items did not predict remission, nor did anxious depression at baseline. In conclusion, among the anxiety/somatization factor items, only early changes in somatic symptoms (gastrointestinal) predicted remission. Future studies are warranted to further investigate this relationship as well as that between anxious depression and treatment outcome.
Cationic nanoparticles for delivery of amphotericin B: preparation, characterization and activity in vitro (2008)

Novel and effective cationic particles delivered amphotericin B to C. albicans in vitro with optimal efficiency seldom achieved from drug, cationic lipid or cationic polyelectrolyte in separate. The multiple assembly of antibiotic, cationic lipid and cationic polyelctrolyte, consecutively nanostructured in each particle produced a strategical and effective attack against the fungus cells.
Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice (2009)

Nonalcoholic fatty liver disease (NAFLD) is an abnormal liver metabolism often observed with insulin resistance and metabolic syndrome. Calorie restriction is a useful treatment for NAFLD and reportedly prolongs the life spans of several species in which sirtuin plays an important role. In this study, we examined whether the activation of SIRT1, a mammalian ortholog of sirtuin, may ameliorate the development of NAFLD. Monosodium glutamate (MSG) mice, which exhibited obesity and insulin resistance, were treated with SRT1720, a specific SIRT1 activator from the age of 6-16 wk. Sixteen-week-old MSG mice exhibited increased liver triglyceride content and elevated levels of aminotransferase. SRT1720 treatment significantly reduced these levels without affecting body weight or food intake. These results suggested that the administration of SRT1720 ameliorated the development of NAFLD in MSG mice. The expressions of lipogenic genes, such as sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase, and the serum lipid profiles, including free fatty acids, were elevated in MSG mice and were reduced by SRT1720 treatment. SRT1720 treatment also reduced the expressions of lipogenic genes in cultured HepG2 cells. Furthermore, SRT1720 treatment decreased the expressions of marker genes for oxidative stress and inflammatory cytokines in the liver of MSG mice. Taken together, SRT1720 treatment may reduce liver lipid accumulation, at least in part, by directly reducing the expressions of lipogenic genes. The reduction of oxidative stress and inflammation may also be involved in the amelioration of NAFLD.
A robust bulk-solvent correction and anisotropic scaling procedure (2005)

A reliable method for the determination of bulk-solvent model parameters and an overall anisotropic scale factor is of increasing importance as structure determination becomes more automated. Current protocols require the manual inspection of refinement results in order to detect errors in the calculation of these parameters. Here, a robust method for determining bulk-solvent and anisotropic scaling parameters in macromolecular refinement is described. The implementation of a maximum-likelihood target function for determining the same parameters is also discussed. The formulas and corresponding derivatives of the likelihood function with respect to the solvent parameters and the components of anisotropic scale matrix are presented. These algorithms are implemented in the CCTBX bulk-solvent correction and scaling module.
Throwing the dice for the diagnosis of vaginal complaints? (2006)

Errors in the diagnosis of BV and candida vulvovaginitis (CV) were high. Interestingly, the cases of misjudgement of CV (77%) were more numerous than that of BV (61%). The use of Amsel criteria or microscopy did not reduce the number of misinterpretations. The study reveals that the misdiagnosis of vaginal complaints is rather high.
Second-harmonic imaging microscopy of living cells (2001)

Second harmonic generation (SHG) has been developed in our laboratories as a high-resolution nonlinear optical imaging microscopy for cellular membranes and intact tissues. SHG shares many of the advantageous features for microscopy of another more established nonlinear optical technique: two-photon excited fluorescence (TPEF). Both are capable of optical sectioning to produce three-dimensional images of thick specimens and both result in less photodamage to living tissue than confocal microscopy. SHG is complementary to TPEF in that it uses a different contrast mechanism and is most easily detected in the transmitted light optical path. It can be used to image membrane probes with high membrane specificity and displays extraordinary sensitivity in reporting membrane potential; it also has the ability to image highly ordered structural proteins without any exogenous labels.
Chronic lithium administration potentiates brain arachidonic acid signaling at rest and during cholinergic activation in awake rats (2003)

Studies were performed to determine if the reported 'proconvulsant' action of lithium in rats given cholinergic drugs is related to receptor-initiated phospholipase A2 signaling via arachidonic acid. Regional brain incorporation coefficients k* of intravenously injected [1-14C]arachidonic acid, which represent this signaling, were measured by quantitative autoradiography in unanesthetized rats at baseline and following administration of subconvulsant doses of the cholinergic muscarinic agonist, arecoline. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, the mean baseline values of k* in brain auditory and visual areas were significantly greater than in rats fed control diet. Arecoline at doses of 2 and 5 mg/kg intraperitoneally increased k* in widespread brain areas in rats fed the control diet as well as the LiCl diet. However, the arecoline-induced increments often were significantly greater in the LiCl-fed than in the control diet-fed rats. Lithium's elevation of baseline k* in auditory and visual regions may correspond to its ability in humans to increase auditory and visual evoked responses. Additionally, its augmentation of the k* responses to arecoline may underlie its reported 'proconvulsant' action with cholinergic drugs, as arachidonic acid and its eicosanoid metabolites can increase neuronal excitability and seizure propagation.
New anticancer agents: in vitro and in vivo evaluation of the antitumor and antimetastatic actions of various compounds isolated from medicinal plants. (2005)

In this review, in the search for the development of new anticancer drugs, the effects of compounds isolated from various medicinal plants on tumor growth and metastasis, using mice bearing a highly metastatic drug-resistant mouse tumor, were studied. The antitumor and antimetastatic actions of stilbene derivatives isolated from Polygonum and Cassia species were examined. Among the stilbene derivatives, resveratrol and cassiagrol A (stilbene dimer) displayed antitumor and antimetastatic actions through the inhibition of tumor-induced neovascularization in in vitro and in vivo models. It was found that two chalcone derivatives from Angelica keiskei roots also inhibited tumor growth and metastasis in tumor-bearing mice through the inhibition of tumor-induced neovascularization and/or the inhibition of immune suppression caused by tumors. Recently, basidiomycete fungi have been used for the treatment of cancer. Then, the low molecular weight substances were isolated from Agaricus blazei and Ganoderma lucidum as antitumor and antimetastatic substances. It is suggested that these substances of basidiomycete also inhibited tumor growth and metastasis to the lung through the inhibition of tumor-induced neovascularization and/or the inhibition of immune suppression caused by tumors.
The role of T-regulatory cells in pregnancy and cancer (2007)

The acceptance of paternally-derived alloantigens during pregnancy and escape from host immunosurveillance by cancer are based on similar immunological mechanisms. Among them both natural and peripherally-induced T CD4+ CD25+ Foxp3+ and Tr1 regulatory cells (Tregs) play important role. Interactions of Tregs with other immunocytes including dendritic cells, mechanisms of Tregs recruitment and their suppressive properties in cancer and pregnancy have been presented in this paper. Despite the fact that mechanisms of Treg regulation are still in progress, there is a hope for use of Tregs-related immunotherapy in clinical practice, and the first attempts of such management have already been described. However, more information about the function of Tregs cells is needed to provide safe treatment devoid of potential side-effects. Resolving the secrets of Tregs cells will probably offer new options of cancer treatment and will help to improve the management of pregnancy failure.