gebhart/patrepeval huggingface dataset:
An Analysis of Urinary Prostate Specific Antigen Before and After Radical Prostatectomy: Evidence for Secretion of Prostate Specific Antigen by the Periurethral Glands (1993)

We investigated whether urinary prostate specific antigen (PSA) might be a useful marker to detect locally recurrent tumor after radical prostatectomy. We also investigated whether PSA in the first 1 to 5 cc of voided urine is a more useful indicator of urinary PSA levels than the midstream urine PSA, since the first portion of the voided urine contains the highest concentration of prostatic and urethral secretions. To determine the response of urinary PSA to radical prostatectomy, we obtained first voided and midstream urine PSA levels in 18 patients with adenocarcinoma of the prostate before and after surgery. Mean first voided urine PSA levels decreased from 915.1 ng./ml. (range 21 to 2,853) preoperatively to 21.4 ng./ml. (range 0.9 to 88) postoperatively, while mean midstream urine PSA levels decreased from 245.9 ng./ml. (range 5 to 1,312) preoperatively to 1.8 ng./ml. (range 0 to 20.4) postoperatively. We also obtained postoperative first voided and midstream urine PSA levels in 9 prostate cancer patients who had undergone radical prostatectomy, and were considered to be cured by rigid clinical and histological criteria. To distinguish bladder versus urethral sources of urinary PSA in patients without a prostate, we additionally studied 11 patients without prostate cancer who had undergone cystoprostatectomy with orthotopic bladder substitution and who had undetectable serum PSA levels by the ultrasensitive assay. In the cured prostatectomy patients the mean first voided urine PSA level was 40.2 ng./ml. (range 2.8 to 100) and the mean midstream urine PSA level was 3.4 ng./ml. (range 0.1 to 15.2), while in the cystoprostatectomy patients these levels were 15.5 ng./ml. (range 0.8 to 49.9) and 1.2 ng./ml. (range 0 to 6.4), respectively. We conclude that the first voided urine sample better reflects local PSA production by the prostate than the midstream sample, first voided urine PSA decreases significantly in response to radical prostatectomy but is still present in measurable amounts even in surgically cured prostate cancer patients and urethral secretion of low levels of PSA persists after radical prostatectomy. This finding diminishes the chance that the first voided urine PSA level will be a useful marker to detect locally recurrent tumor after radical prostatectomy. Further studies are needed to determine if there is a critical level of first voided urine PSA after radical prostatectomy above which there is an increased likelihood of locally recurrent tumor but overall urinary PSA is highly unlikely to be clinically useful.
CpG Oligodeoxynucleotides Down-Regulate Macrophage Class II MHC Antigen Processing (1999)

Unmethylated CpG motifs in bacterial DNA or short oligodeoxynucleotides (ODN) stimulate cells of the immune system and provide adjuvant activity. CpG DNA directly activates macrophages to secrete IL-12 and TNF-alpha and increases transcription of various genes, but its effects on macrophage Ag processing remain uncertain. The effects of CpG ODN on class II MHC (MHC-II) Ag processing and presentation were examined using peritoneal macrophages that were cultured for 18 h with CpG ODN and then pulsed with protein Ags. T cell hybridomas were used to detect presentation of specific peptide:MHC-II complexes. Both CpG ODN and LPS inhibited processing of bovine RNase and hen egg lysozyme. Presentation of exogenous peptides was inhibited to a lesser degree. Treatment of macrophages for 18 h with CpG ODN decreased surface MHC-II expression, as measured by flow cytometry. Furthermore, Northern blot analysis revealed that treatment with CpG ODN decreased I-Ak mRNA. Endocytosis by macrophages, as measured by uptake of fluorescent dextran, was not altered by treatment with CpG ODN. The inhibitory effect of CpG ODN on Ag processing was seen after prolonged (18 h) treatment of macrophages, but not after short treatment (e.g., 2 h) with CpG ODN and protein Ag. Enhancement of macrophage Ag processing was not seen at any time point of CpG ODN exposure, in contrast to data from other studies with dendritic cells. In summary, exposure of macrophages to CpG ODN results in a decrease in macrophage Ag processing and presentation, which is largely mediated by a decrease in synthesis of MHC-II molecules.
Acid-sensing ion channels in healthy and degenerated human intervertebral disc (2014)

Acid-sensing ion channels (ASICs) are a family of H(+)-gated voltage-insensitive ion channels that respond to extracellular acidification by regulating transmembrane Ca(2+) flux. Moreover, ASICs can also be gated by mechanical forces and may function as mechanosensors. The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. Changes in the pH and osmolarity determine the viability of IVD cells and the composition of the extracellular matrix, and both are the basis of IVD degeneration. In this study, the expression of ASICs (ASIC1, ASIC2, ASIC3 and ASIC4) mRNAs and proteins in human healthy and degenerated IVD was evaluated by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot. The distribution of ASIC proteins was determined by immunohistochemistry. The mRNAs for all ASICs were detected in normal human IVD, and significantly increased levels were found in degenerated IVD. Western blots demonstrated the presence of proteins with estimated molecular weights of approximately 68-72 kDa. In both the annulus fibrosus (AF) and nucleus pulposus (NP) of normal IVD, ASIC2 is the most frequently expressed ASIC followed by ASIC3, ASIC1 and ASIC4. In the AF of degenerated IVD, there was a significant increase in the number of ASIC1 and ASIC4 positive cells, whereas in the NP, we found significant increase of expression of ASIC1, ASIC2 and ASIC3. These results describe the occurrence and localization of different ASICs in human healthy IVD, and their increased expression in degenerated IVD, thus suggesting that ASICs may be involved in IVD degeneration.
Cooperation between Helper T Cells and Cytotoxic T Lymphocyte Precursors (1988)

We have investigated the requirement for the presence of L3T4-positive T cells in the in vivo priming of Lyt-2-positive cytotoxic T-lymphocyte precursors. The antigens used were the male-specific antigen H-Y and autosomal minor histocompatibility antigens. In some experiments, responder mice were depleted of L3T4-positive cells by repeated intraperitoneal injections of the anti-L3T4 antibody, GK1.5. In other experiments, lymphoid cells from normal mice were fractionated in vitro by antibody-plus-complement treatment and the populations primed in irradiated adoptive hosts. In these antigen systems, depletion of L3T4-positive helper cells decreases the level of priming of cytotoxic T lymphocytes. With regeneration of the L3T4-positive subpopulation, the CTL response to antigen increases. To some extent, the reliance on L3T4-positive cells can be overcome by increasing the antigen dose. We conclude that in most physiological responses, L3T4-positive T cells enhance the cytotoxic T-cell response.
Optogenetic approaches addressing extracellular modulation of neural excitability (2016)

The extracellular ionic environment in neural tissue has the capacity to influence, and be influenced by, natural bouts of neural activity. We employed optogenetic approaches to control and investigate these interactions within and between cells, and across spatial scales. We began by developing a temporally precise means to study microdomain-scale interactions between extracellular protons and acid-sensing ion channels (ASICs). By coupling single-component proton-transporting optogenetic tools to ASICs to create two-component optogenetic constructs (TCOs), we found that acidification of the local extracellular membrane surface by a light-activated proton pump recruited a slow inward ASIC current, which required molecular proximity of the two components on the membrane. To elicit more global effects of activity modulation on 'bystander' neurons not under direct control, we used densely-expressed depolarizing (ChR2) or hyperpolarizing (eArch3.0, eNpHR3.0) tools to create a slow non-synaptic membrane current in bystander neurons, which matched the current direction seen in the directly modulated neurons. Extracellular protons played contributory role but were insufficient to explain the entire bystander effect, suggesting the recruitment of other mechanisms. Together, these findings present a new approach to the engineering of multicomponent optogenetic tools to manipulate ionic microdomains, and probe the complex neuronal-extracellular space interactions that regulate neural excitability.
Hierarchically Structured Nanocomposite Films as Highly Sensitive Chemosensory Materials for TNT Detection (2006)

Sensitive to TNT vapor: Porphyrin-doped silica films with bimodal porous structures, fabricated using a dual template approach, exhibit remarkable sensitivity towards traces of TNT vapour. These hierarchically structured nanocomposites serve as useful chemosensory materials for rapid detection of explosives (see picture).
Implementing a mainframe coding/abstracting system. (1992)

In conclusion, the successful implementation of a medical record abstracting system was realized due to the following factors: extensive planning, thorough organization of tasks, controlled implementation, and ongoing controls. While thorough planning and organization will result in an efficient implementation, ongoing controls will ensure continued success and produce high quality results for any medical record system.
Differential Role of Melanocortin Receptor Subtypes in Cachexia (2003)

Animals and humans respond to starvation with a complex neuroendocrine response that ultimately leads to an increase in appetite, a sparing of lean body mass (LBM) and burning of fat, and an overall decrease in basal metabolic rate. In contrast, cachexia is a pathological state of malnutrition associated with many infections and chronic diseases, wherein appetite is diminished concomitant with an increase in metabolic rate, and a relative wasting of LBM. In previous studies, we demonstrated that anorexia and weight loss in mouse cachexia models induced by lipopolysaccharide (LPS) administration and by tumor growth are ameliorated by central melanocortin-4 (MC4) receptor (MC4-R) blockade. In contrast to the results seen with MC4 blockade, melanocortin-3 (MC3) receptor knockout (MC3-RKO) mice show illness-induced anorexia and weight loss with LPS administration and with cytokine administration, and they have similar decreases in mobility. Both MC3-RKOs and MC4-RKOs have an intact corticosterone response and fever with LPS injection. In tumor models, we show that MC4-RKO mice resist the loss of LBM brought about by tumor growth, whereas MC3-RKO animals show enhanced tissue wasting. These data underscore the importance of central melanocortin signaling in weight homeostasis and demonstrate differential effects of MC3-R and MC4-R blockade on the development of cachexia.
Comparative effects of mu and kappa opiate agonists on the cecocolic motility in the pony. (1994)

The electrical and mechanical activity of the large intestine and its response to administration of opiate mu and kappa agonists were assessed from electrodes and inductograph coils chronically implanted on the cecocolic segment in six ponies given a diet of hay and concentrates. Before the drugs were given, migrating complexes propagating from the cecum into the colon occurred at the rate of 1.5 to 16/hour. During this propulsive activity, the cecocolic sphincter opened and closed allowing the outflow of cecal contents and preventing the backflow of colic contents. Each pony was used as its own control and was given fentanyl (0.01 and 0.05 mg/kg of body weight, IV) and U50488H (0.1 and 0.5 mg/kg, IV) at weekly intervals. The mu agonist fentanyl elicited a marked phase of inhibition of the propulsive activity and a closure of the cecocolic sphincter that lasted one to two hours depending on the dose. The kappa agonist U50488H induced an inhibition of the short spiking activity, i.e. of the resting muscle tone. It did not disturb the occurrence of migrating complexes nor that of the openings of the cecocolic sphincter. These kappa compounds may be drugs of choice to alleviate visceral pain in colic stases without inducing delay of transit unlike mu compounds.
How the brain might work: a hierarchical and temporal model for learning and recognition (2008)

The brains of mammals are very efficient learning machines. Many aspects of mammalian learning are yet to be incorporated into machine learning algorithms. For instance, vision is typically considered to be a spatial problem in which a learning system needs to be trained with labeled examples of object images. Yet, mammals learn with continuously flowing unlabeled data. It is also generally accepted that the visual cortex in mammals is organized as a hierarchy and that many aspects of visual perception can be modeled using Bayesian computations. 
This dissertation introduces algorithms and networks that combine hierarchical and temporal learning with Bayesian inference for pattern recognition. These algorithms and networks, collectively called Hierarchical Temporal Memory (HTM), can be used to learn hierarchical-temporal models of data. Temporal continuity is used to learn multiple levels of the hierarchy without supervision. The HTM algorithms, when applied to a visual pattern recognition problem, exhibit invariant recognition, robustness to noise, and generalization. Inference in the hierarchy is performed using Bayesian belief propagation equations that are adapted to this problem setting. 
In order to understand the generalization properties of HTMs, a generative model for HTMs is developed. This model enables the generation of synthetic data from HTM networks. These data are used to analyze and characterize learning and generalization in hierarchical-temporal systems. Two existing hierarchical pattern recognition models are mapped to HTMs to explain the source of generalization in those models. 
Finally, the HTM Bayesian belief propagation equations are used to suggest a mathematical model for cortical microcircuits. The microcircuit model is derived by combining known anatomical constraints with the computational specifications of HTM belief propagation. The proposed model has a laminar and columnar organization that matches many known anatomical features. The proposed circuits are then used in the modeling of two well known physiological phenomena.
Sol-Gel Synthesis of SiO&lt;sub&gt;2&lt;/sub&gt;-CaO-Na&lt;sub&gt;2&lt;/sub&gt;O-P&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;5&lt;/sub&gt; Bioactive Glass Ceramic from Sodium Metasilicate (2013)

Bioactive glass ceramic with SiO2-Ca2O-Na2O-P2O5 composition was prepared by the sol-gel method using sodium metasilicate (Na2SiO3) as silica source. The monolith obtained was sintered at 1000?C for 2 hours after which X-ray diffraction (XRD) analysis showed presence of combeite (Na2Ca2Si3O9) as the crystalline phase. In vitro bioactivity test conducted on the material using simulated body fluid (SBF) showed the formation of carbonated hydroxyapatite on its surface. The material during the SBF test was observed to transform from a mechanically strong crystalline phase Na2Ca2Si3O9 to an amorphous phase after incubation for 14 days indicating that the material was biodegradable. Scanning electron microscopy (SEM) was used to investigate the surface morphology, while Fourier transform infrared (FTIR) spectroscopy facilitated the confirmation of hydroxyapatite (HA) formation. The monolith material obtained may be a good candidate for application in tissue engineering scaffolds.
In Vivo Imaging of Human Malignant Mesothelioma Grown Orthotopically in the Peritoneal Cavity of Nude Mice (2011)

Malignant mesothelioma (MM) causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP) fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL) that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo.
Radioimmunotherapy with iodine 131I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience (2000)

CD20-targeted radioimmunotherapy is a promising new treatment for B-cell non-Hodgkin lymphoma (NHL). We now provide updated and long-term data on 59 chemotherapy-relapsed/refractory patients treated with iodine (131)I tositumomab in a phase I/II single-center study. Fifty-three patients received individualized therapeutic doses, delivering a specified total-body radiation dose (TBD) based on the clearance rate of a preceding dosimetric dose. Six patients received dosimetric doses only. Dose-escalations of TBD were conducted separately in patients who had or had not undergone a prior autologous stem cell transplant (ASCT) until a nonmyeloablative maximally tolerated TBD was established (non-ASCT = 75 cGy, post-ASCT = 45 cGy). Fourteen additional non-ASCT patients were treated with 75 cGy. Unlabeled antibody was given prior to labeled dosimetric and therapeutic doses to improve biodistribution. Forty-two (71%) of 59 patients responded; 20 (34%) had complete responses (CR). Thirty-five (83%) of 42 with low-grade or transformed NHL responded versus 7 (41%) of 17 with de novo intermediate-grade NHL (P =.005). For all 42 responders, the median progression-free survival was 12 months, 20.3 for those with CR. Seven patients remain in CR 3 to 5.7 years. Sixteen patients were re-treated after progression; 9 responded and 5 had a CR. Reversible hematologic toxicity was dose limiting. Only 10 patients (17%) had human anti-mouse antibodies detected. Long-term, 5 patients developed elevated thyroid-stimulating hormone levels, 5 were diagnosed with myelodysplasia and 3 with solid tumors. A single, well-tolerated treatment with iodine (131)I tositumomab can, therefore, produce frequent and durable responses in NHL, especially low-grade or transformed NHL. (Blood. 2000;96:1259-1266)
Structural Differences between Wild-Type and Double Mutant EGFR Modulated by Third-Generation Kinase Inhibitors (2015)

Mutations in the EGFR kinase domain are implicated in non-small-cell lung cancer. Of particular interest is the drug-resistant double mutant (L858R/T790M, DM EGFR), which is not inhibited selectively by any approved kinase inhibitor. Here we apply bipartite tetracysteine display to demonstrate that DM and WT EGFR differ in structure outside the kinase domain. The structural difference is located within the cytoplasmic juxtamembrane segment (JM) that links the kinase domain with the extracellular and transmembrane regions and is essential for EGFR activation. We show further that third-generation DM EGFR-selective TKIs alter JM structure via allostery to restore the conformation found when WT EGFR is activated by the growth factors EGF and HB-EGF. This work suggests that the oncogenic activity of DM EGFR may extend beyond kinase activity per se to include kinase-independent activities. As JM structure may provide a biomarker for these kinase-independent functions, these insights could guide the development of allosteric, DM-selective inhibitors.
Molecular mechanism of action of parathyroid hormone related peptide in hypercalcemia of malignancy: therapeutic strategies (review). (2000)

Parathyroid hormone related peptide (PTHRP) was identified and characterized from tumors manifesting the syndrome of hypercalcemia of malignancy (HM). These hypercalcemic effects are due to the strong sequence homology between parathyroid hormone (PTH) and PTHRP in the bioactive amino terminal region and its ability to interact with G-protein linked seven transmembrane PTH/PTHRP receptor. However, due to the expression of PTHRP in several fetal and adult tissues, it also has a variety of physiological actions including the ability to play an important role in cell growth and differentiation. Since the isolation and characterization of PTHRP gene, intense efforts have been made to study its circulating forms in health and disease, regulation of PTHRP gene expression and molecular mechanism of PTHRP action in normal and in tumor cells. Various in vivo models of HM were developed which mimicked the human syndrome. Mice homozygous for PTHRP deletion died at birth due to impaired chondrocyte differentiation resulting in skeletal deformities and respiratory failure. Since HM continues to be a major cause of cancer associated morbidity and mortality there is an urgent need to develop strategies to control the syndrome of HM. This review describes the biosynthesis and secretion of various molecular forms of PTHRP, regulation of PTHRP gene expression and discusses the molecular pathways involved in its actions. Based on this information, various therapeutic strategies which are currently under development are discussed. These studies will form the basis of future efforts aimed at optimization of these approaches for further clinical development.
Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection (2012)

The herpes simplex type 2 (HSV-2) envelope glycoprotein (gD2) was evaluated as a potential antigen candidate for a plasmid DNA (pDNA)-based HSV-2 vaccine. The pDNA was formulated with Vaxfectin, a cationic lipid-based adjuvant, and tested in a murine HSV-2 lethal challenge model. gD2 was expressed as full-length (FL) and secreted (S) gD2 forms. A 0.1 µg pDNA dose was tested to distinguish treatment conditions for survival and a 100 µg pDNA dose was tested to distinguish treatment conditions for reduction in vaginal and latent HSV-2 copies. Vaxfectin-formulated gD2 pDNA significantly increased serum IgG titres and survival for both FL gD2 and S gD2 compared with gD2 pDNA alone. Mice immunized with FL gD2 formulated with Vaxfectin showed reduction in vaginal and dorsal root ganglia (DRG) HSV-2 copies. The stringency of this protection was further evaluated by testing Vaxfectin-formulated FL gD2 pDNA at a high 500 LD(50) inoculum. At this high viral challenge, the 0.1 µg dose of FL gD2 Vaxfectin-formulated pDNA yielded 80 % survival compared with no survival for FL gD2 pDNA alone. Vaxfectin-formulated FL gD2 pDNA, administered at a 100 µg pDNA dose, significantly reduced HSV-2 DNA copy number, compared with FL gD2 DNA alone. In addition, 40 % of mice vaccinated with adjuvanted FL pDNA had no detectable HSV-2 viral genomes in the DRG, whereas all mice vaccinated with gD2 pDNA alone were positive for HSV-2 viral genomes. These results show the potential contribution of Vaxfectin-gD2 pDNA to a future multivalent HSV-2 vaccine.