gebhart/patrepeval huggingface dataset:
Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity (2003)

Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency.
Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic stenotic valves (2002)

Aortic Valve Stenosis (AVS) has been explained as an atherosclerotic process of the valve as they often exhibit inflammatory changes with infiltration of macrophages, T lymphocytes and lipid infiltration. The present study investigated whether the bacteria Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP), detected previously in atherosclerotic plaques, are also present in AVS. Ten valves surgically removed from patients with AVS were analyzed by immunohistochemistry, in situ hybridization, and electron microscopy. The mean and standard deviation of the percentage areas occupied by CP antigens and MP - DNA were respectively 6.21 +/- 5.41 and 2.27 +/- 2.06 in calcified foci; 2.8 +/- 3.33 and 1.78+/- 3.63 in surrounding fibrotic areas, and 0.21 +/- 0.17 and 0.12 +/- 0.13 in less injured parts of the valve. There was higher amount of CP and MP in the calcified foci and in the surrounded fibrosis than in more preserved valvular regions. In conclusion, the fact that there were greater amounts of CP and MP in calcification foci of AVS favors the hypothesis that AS is not an inevitable degenerative process due to aging, but rather that it may be a response to the presence of these bacteria, similarly to the morphology detected in atherosclerosis damage.
Serotonergic Responsivity in Obsessive-Compulsive Disorder (1987)

To examine the "serotonin hypothesis" of obsessive-compulsive disorder (OCD), we studied the behavioral and neuroendocrine effects of metachlorophenylpiperazine (mCPP), a serotonergic agonist, in patients with OCD and healthy controls. Twelve patients and 20 controls were given a single dose of 0.5 mg/kg of mCPP, administered orally under double-blind, placebo-controlled, random-assignment conditions. Following mCPP, but not following placebo, patients with OCD experienced a transient but marked exacerbation of obsessive-compulsive symptoms. Moreover, compared with healthy controls, patients exhibited greater other behavioral (but not endocrinologic or thermal) changes after mCPP. These findings are consistent with a special role for the neurotransmitter serotonin in OCD psychopathology.
Low-Dose Paclitaxel Prior to Intratumoral Dendritic Cell Vaccine Modulates Intratumoral Cytokine Network and Lung Cancer Growth (2007)

Our data indicate that low-dose chemotherapy before intratumoral delivery of dendritic cells might be associated with beneficial alterations of the intratumoral microenvironment and thus support antitumor immunity.
Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate. (1994)

Phenylacetate is a naturally occurring plasma component that suppresses the growth of tumor cells and induces differentiation in vitro. To evaluate the in vivo potential and preventive and therapeutic antitumor efficacy of sodium phenylacetate against malignant brain tumors, Fischer 344 rats (n = 50) bearing cerebral 9L gliosarcomas received phenylacetate by continuous s.c. release starting on the day of tumor inoculation (n = 10) using s.c. osmotic minipumps (550 mg/kg/day for 28 days). Rats with established brain tumors (n = 12) received continuous s.c. phenylacetate supplemented with additional daily i.p. dose (300 mg/kg). Control rats (n = 25) were treated in a similar way with saline. Rats were sacrificed during treatment for electron microscopic studies of their tumors, in vivo proliferation assays, and measurement of phenylacetate levels in the serum and cerebrospinal fluid. Treatment with phenylacetate extended survival when started on the day of tumor inoculation (P < 0.01) or 7 days after inoculation (P < 0.03) without any associated adverse effects. In the latter group, phenylacetate levels in pooled serum and cerebrospinal fluid samples after 7 days of treatment were in the therapeutic range as determined in vitro (2.45 mM in serum and 3.1 mM in cerebrospinal fluid). Electron microscopy of treated tumors demonstrated marked hypertrophy and organization of the rough endoplasmic reticulum, indicating cell differentiation, in contrast to the scant and randomly distributed endoplasmic reticulum in tumors from untreated animals. In addition, in vitro studies demonstrated dose-dependent inhibition of the rate of tumor proliferation and restoration of anchorage dependency, a marker of phenotypic reversion. Phenylacetate, used at clinically achievable concentrations, prolongs survival of rats with malignant brain tumors through induction of tumor differentiation. Its role in the treatment of brain tumors and other cancers should be explored further.
Community-based health reporting. (1988)

A development monitoring service at the local level was established in 1978/79 in several communities in Kerala State (India) to collect socioeconomic and health-related data. These were collected from key community members and by household surveys using paid local staff as interviewers. Selected results for five years from three geographically distinct areas are presented, for three categories of data: health service infrastructure, infant mortality and overall morbidity, and weight and height of children under 10 years old. The three areas were a fishing village (A), a relatively remote highland community (B) and an agricultural area close to the state capital (C). During the five-year period there were rather modest improvements in the delivery of health and other services. Infant mortality rates fluctuated between 14 and 91 per 1,000 live births, reflecting the fact that the sample size (10,000 to around 25,000 for each area) was inadequate for calculating that rate. Morbidity rates also fluctuated markedly, without showing any definite trend. However, morbidity was defined as illness resulting in the inability to carry out normal activities, thus excluding cases of worm infestation and much diarrhoea, for example. A detailed analysis of reported symptoms for one year showed that respiratory tract diseases accounted for about half the cases of illness reported. The percentage of children with abnormally low weight- or height-for-age fell markedly in one area over three successive years (height-for-age from 41.6% to 33.2%, weight-for-age from 58.5% to 44.7%), but were significantly greater in another area with a higher average income, indicating that economic factors alone were not responsible for the improvement.(ABSTRACT TRUNCATED AT 250 WORDS)
Histone Deacetylase Inhibitor Downregulation of bcl-xl Gene Expression Leads to Apoptotic Cell Death in Mesothelioma (2001)

It has been shown that mesothelioma expresses the antiapoptotic protein BCL-XL, but not BCL-2, rendering bcl-xl gene expression a potential therapeutic target. Sodium butyrate (NaB) is a histone deacetylase inhibitor capable of alteration of bcl-2 family protein expression in other tumor types. Mesothelioma cell lines (REN, I-45) were exposed to NaB, and viability (colorimetric assay) and apoptosis (TUNEL, Hoescht staining, flow cytometry) were evaluated. Effects on bcl-2 family protein, fas-fas ligand, and caspases were examined by Western blot analysis and functional assay. An RNase assay evaluated bcl-2 family messenger RNA (mRNA) expression. Overexpressing BCL-XL mesothelioma clones were created by plasmid transfer. Cells were sensitive to NaB at low IC(50) (REN, 0.3 mM; I-45, 1 mM) and demonstrated apoptosis (percentage of cells below G1 phase by flow cytometry [sub-G1]: REN, 38.5%; I-45, 30.9%). A significant decrease in BCL-XL protein expression was noted with BAK, BAX, and BCL-2 unchanged, and this was corroborated at the transcriptional level with selectively decreased bcl-xl mRNA production after sodium butyrate exposure. Fas expression and fas-fas ligand sensitivity were unchanged. Caspases demonstrated low-level activation. Stable overexpressing BCL-XL clones were proportionally resistant to the NaB effect. This study suggests that mesothelioma cells are sensitive to the induction of apoptosis related to the attenuation of antiapoptotic bcl-xl gene and protein expression. Additional study of the therapeutic benefit of targeting bcl-xl gene expression in mesothelioma is warranted.
Tree‐based disease classification using protein data (2003)

A reliable and precise classification of diseases is essential for successful diagnosis and treatment. Using mass spectrometry from clinical specimens, scientists may find the protein variations among disease and use this information to improve diagnosis. In this paper, we propose a novel procedure to classify disease status based on the protein data from mass spectrometry. Our new tree-based algorithm consists of three steps: projection, selection and classification tree. The projection step aims to project all observations from specimens into the same bases so that the projected data have fixed coordinates. Thus, for each specimen, we obtain a large vector of 'coefficients' on the same basis. The purpose of the selection step is data reduction by condensing the large vector from the projection step into a much lower order of informative vector. Finally, using these reduced vectors, we apply recursive partitioning to construct an informative classification tree. This method has been successfully applied to protein data, provided by the Department of Radiology and Chemistry at Duke University.
Tissue Factor Pathway Inhibitor and Thrombin Activatable Fibrinolytic Inhibitor Plasma Levels following Burnand Septic Injuries in Rats (2004)

Burn and septic injuries induce profound changes in coagulation status. This study examined the changes in plasma tissue factor pathway inhibitor (TFPI) and thrombin activatable fibrinolytic inhibitor (TAFI) levels in a rat model of burn and septic injuries. Rats underwent 30% TBSA cutaneous scald burn injury and septic insult was induced by caecal ligation and puncture (CLP). CLP was superimposed on burn injury to mimic the clinical model of sepsis complicating burn injury. Rats were pretreated with Cprofloxacin orally to colonize their gut with Enterococcus faecalis. TFPI and TAFI plasma levels were measured using functional activity assay kit with a chromogenic method at 24 and 72 hours following the injuries. TFPI levels decreased significantly at 24 hours in burn, CLP, and burn+CLP groups, followed by incomplete rebound recovery at 72 hours in all three groups. On the other hand, TAFI levels increased significantly at 24- and 72-hour time points in all three groups. These results suggest that burn, septic, and their combined injuries perturb coagulation cascade and thrombotic process toward the procoagulant pathway by impairing fibrinolysis.
A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo1[S] (2010)

Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) regulates LDL cholesterol levels by inhibiting LDL receptor (LDLr)-mediated cellular LDL uptake. We have identified a fragment antigen-binding (Fab) 1D05 which binds PCSK9 with nanomolar affinity. The fully human antibody 1D05-IgG2 completely blocks the inhibitory effects of wild-type PCSK9 and two gain-of-function human PCSK9 mutants, S127R and D374Y. The crystal structure of 1D05-Fab bound to PCSK9 reveals that 1D05-Fab binds to an epitope on the PCSK9 catalytic domain which includes the entire LDLr EGF(A) binding site. Notably, the 1D05-Fab CDR-H3 and CDR-H2 loops structurally mimic the EGF(A) domain of LDLr. In a transgenic mouse model (CETP/LDLr-hemi), in which plasma lipid and PCSK9 profiles are comparable to those of humans, 1D05-IgG2 reduces plasma LDL cholesterol to 40% and raises hepatic LDLr protein levels approximately fivefold. Similarly, in healthy rhesus monkeys, 1D05-IgG2 effectively reduced LDL cholesterol 20%-50% for over 2 weeks, despite its relatively short terminal half-life (t(1/2) = 3.2 days). Importantly, the decrease in circulating LDL cholesterol corresponds closely to the reduction in free PCSK9 levels. Together these results clearly demonstrate that the LDL-lowering effect of the neutralizing anti-PCSK9 1D05-IgG2 antibody is mediated by reducing the amount of PCSK9 that can bind to the LDLr.
Direct Inhibition of Cyclooxygenase-1 and -2 by the Kinase Inhibitors SB 203580 and PD 98059 (1998)

The kinase inhibitors SB 203580 and PD 98059 have been reported to be specific inhibitors of the 38- and 42/44-kDa mitogen-activated protein kinase (MAPK) pathways, respectively. In this study, the two inhibitors were found to decrease platelet aggregation induced by low concentrations of arachidonic acid, suggesting that they also interfere with the metabolism of arachidonic acid to thromboxane A2. In support of this, SB 203580 and PD 98059 inhibited the conversion of exogenous [3H]arachidonic acid to [3H]thromboxane in intact platelets. Measurement of platelet cyclooxygenase-1 activity following immunoprecipitation revealed that SB 203580 and PD 98059 are direct inhibitors of this enzyme. Both compounds were shown to inhibit purified cyclooxygenase-1 and -2 by a reversible mechanism. In addition, SB 203580 (but not PD 98059) inhibited platelet aggregation induced by prostaglandin H2 and the conversion of prostaglandin H2 to thromboxane A2 in intact platelets. SB 203580 also inhibited this pathway in platelet microsome preparations, suggesting a direct inhibitory effect on thromboxane synthase. These results demonstrate that direct effects of the two kinase inhibitors on active arachidonic acid metabolites have to be excluded before using these compounds for the investigation of MAPKs in signal transduction pathways. This is of particular relevance to studies on the regulation of cytosolic phospholipase A2 as these two MAPKs are capable of phosphorylating cytosolic phospholipase A2, thereby increasing its intrinsic activity.
Cognition and the Placebo Effect – Dissociating Subjective Perception and Actual Performance (2015)

The influence of positive or negative expectations on clinical outcomes such as pain relief or motor performance in patients and healthy participants has been extensively investigated for years. Such research promises potential benefit for patient treatment by deliberately using expectations as means to stimulate endogenous regulation processes. Especially regarding recent interest and controversies revolving around cognitive enhancement, the question remains whether mere expectancies might also yield enhancing or impairing effects in the cognitive domain, i.e., can we improve or impair cognitive performance simply by creating a strong expectancy in participants about their performance? Moreover, previous literature suggests that especially subjective perception is highly susceptible to expectancy effects, whereas objective measures can be affected in certain domains, but not in others. Does such a dissociation of objective measures and subjective perception also apply to cognitive placebo and nocebo effects? In this study, we sought to investigate whether placebo and nocebo effects can be evoked in cognitive tasks, and whether these effects influence objective and subjective measures alike. To this end, we instructed participants about alleged effects of different tone frequencies (high, intermediate, low) on brain activity and cognitive functions. We paired each tone with specific success rates in a Flanker task paradigm as a preliminary conditioning procedure, adapted from research on placebo hypoalgesia. In a subsequent test phase, we measured reaction times and success rates in different expectancy conditions (placebo, nocebo, and control) and then asked participants how the different tone frequencies affected their performance. Interestingly, we found no effects of expectation on objective measures, but a strong effect on subjective perception, i.e., although actual performance was not affected by expectancy, participants strongly believed that the placebo tone frequency improved their performance.
Siderophores in Fungal Physiology and Virulence (2008)

Maintaining the appropriate balance of iron between deficiency and toxicity requires fine-tuned control of systems for iron uptake and storage. Both among fungal species and within a single species, different systems for acquisition, storage, and regulation of iron are present. Here we discuss the most recent findings on the mechanisms involved in maintaining iron homeostasis with a focus on siderophores, low-molecular-mass iron chelators, employed for iron uptake and storage. Recently siderophores have been found to be crucial for pathogenicity of animal, as well as plant-pathogenic fungi and for maintenance of plant-fungal symbioses.
Epitaxial BiFeO 3 Multiferroic Thin Film Heterostructures (2003)

Enhancement of polarization and related properties in heteroepitaxially constrained thin films of the ferroelectromagnet, BiFeO3, is reported. Structure analysis indicates that the crystal structure of film is monoclinic in contrast to bulk, which is rhombohedral. The films display a room-temperature spontaneous polarization (50 to 60 microcoulombs per square centimeter) almost an order of magnitude higher than that of the bulk (6.1 microcoulombs per square centimeter). The observed enhancement is corroborated by first-principles calculations and found to originate from a high sensitivity of the polarization to small changes in lattice parameters. The films also exhibit enhanced thickness-dependent magnetism compared with the bulk. These enhanced and combined functional responses in thin film form present an opportunity to create and implement thin film devices that actively couple the magnetic and ferroelectric order parameters.
Optimizing headache care for the individual patient (2010)

Abstract This chapter aims to cover the existing knowledge on the diagnostic procedure, treatment strategy, and the assessment of outcome for individuals seeking medical help. Furthermore, it aims at providing some ideas for future analysis of outcome and strategy.
Fluorescence spectra provide information on the depth of fluorescent lesions in tissue (2005)

The fluorescence spectrum measured from a fluorophore in tissue is affected by the absorption and scattering properties of the tissue, as well as by the measurement geometry. We analyze this effect with Monte Carlo simulations and by measurements on phantoms. The spectral changes can be used to estimate the depth of a fluorescent lesion embedded in the tissue by measurement of the fluorescence signal in different wavelength bands. By taking the ratio between the signals at two wavelengths, we show that it is possible to determine the depth of the lesion. Simulations were performed and validated by measurements on a phantom in the wavelength range 815-930 nm. The depth of a fluorescing layer could be determined with 0.6-mm accuracy down to at least a depth of 10 mm. Monte Carlo simulations were also performed for different tissue types of various composition. The results indicate that depth estimation of a lesion should be possible with 2-3-mm accuracy, with no assumptions made about the optical properties, for a wide range of tissues.
Accuracy of Physical Examination, Ultrasonography, and Mammography in Predicting Residual Pathologic Tumor Size in Patients Treated With Neoadjuvant Chemotherapy (2006)

Physical examination, ultrasonography, and mammography were only moderately useful for predicting residual pathologic tumor size after neoadjuvant chemotherapy.
Faecal microbiota composition and host–microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome (2013)

The faecal microbiota of patients with PI-IBS differs from that of healthy controls and resembles that of patients with IBS-D, suggesting a common pathophysiology. Moreover, our analysis suggests a variety of host-microbe associations that may underlie intestinal symptoms, initiated by gastroenteritis.
Studies on epidermal growth factor and the porcine upper gastrointestinal tract (1991)

The factors controlling growth and maturation in the porcine gastrointestinal tract are not well-understood. Epidermal growth factor (EGF) is a polypeptide which has been implicated in the control of gastrointestinal growth, maturation, and protection in other species. The objective of these studies was to gain an understanding of the role that EGF might play in the upper gastrointestinal tract of young pigs by (1) quantifying EGF-like activity in porcine mammary secretions, (2) determining the effect of ingested EGF on jejunal disaccharidases in weanlings, and (3) identifying immunoreactive EGF (IR-EGF) and EGF receptors (EGF-R) in tissues of the upper digestive tract. Through the use of a radioreceptor assay, EGF-like activity was detected at high levels in colostrum and at significantly (P $\le$ 0.01) lower, unchanging concentrations in milk collected 9, 18, and 27 days postpartum. EGF administered orally to 21-day-old weanling pigs beginning the day of weaning, significantly (P $\le$ 0.05) increased jejunal lactase and sucrase activities on the third postweaning day when compared to weanling controls. In the third study, IR-EGF and EGF-R were immunohistochemically identified in formalin-fixed tissues of pigs which were 1-, 3-, 7-, 14-, 21-, and 28-days-old. The ductal epithelium consistently contained IR-EGF in the parotid salivary gland of all ages and in the mandibular salivary gland in pigs 7 days of age and older. Immunoreactive EGF was present in the mucosal epithelium of the esophagus and non-glandular stomach, and in the pancreas and liver in all pigs. Gastric gland IR-EGF was inconsistently present in pigs less than 14 days of age and routinely present thereafter. Enterocyte EGF immunoreactivity was usually weak and variably present in the duodenum of pigs 7 days old and less, in the jejunum of pigs 14 days and less, and was consistently observed in older pigs. Ileal reactivity was erratic. Immunoreactive EGF-R were present in the esophageal epithelium of all pigs, and in the non-glandular gastric and glandular gastric mucosae of all pigs except for two 7 day pigs and one 7 day pig, respectively. Immunoreactive EGF-R were detected in the duodenal, jejunal, and ileal enterocytes of all ages of pigs examined.