gebhart/patrepeval huggingface dataset:
Metal Binding Properties of a Monoclonal Antibody Directed toward Metal-Chelate Complexes (1996)

A monoclonal antibody that recognizes cadmium-EDTA complexes has been produced by the injection of BALB/c mice with a metal-chelate complex covalently coupled to a carrier protein. The ability of purified antibody to recognize 16 different metal-EDTA complexes was assessed by measuring equilibrium binding constants using a KinExATM immunoassay instrument. The antibody bound to cadmium- and mercury-EDTA complexes with equilibrium dissociation constants of 21 and 26 nM, respectively. All other metal-EDTA complexes tested, including those of Mn(II), In(III), Ni(II), Zn(II), Co(II), Cu(II), Ag(I), Fe(III), Pb(II), Au(III), Tb(III), Ga(III), Mg(II), and Al(III) bound with affinities from 20- to 40,000-fold less than that determined for the cadmium-EDTA complex. With the exception of mercury and magnesium, the binding of divalent metal-chelate complexes was well-correlated with the size of the metal ion. The amino acid sequences of the heavy and light chain variable regions were deduced from polymerase chain reaction-amplified regions of the corresponding genes and subsequently used to construct molecular models of the antigen binding region. The key residue for cadmium binding in the model for 2A81G5 appeared to be histidine 96 in the heavy chain.
Reevaluation and Identification of the Best Immunohistochemical Panel (pVHL, Maspin, S100P, IMP-3) for Ductal Adenocarcinoma of the Pancreas (2012)

pVHL, maspin, S100P, and IMP-3 constitute the best diagnostic panel of immunomarkers for confirming the diagnosis of pancreatic ductal adenocarcinoma in both surgical and fine-needle aspiration specimens.
Enhanced antitumor efficiency of docetaxel-loaded nanoparticles in a human ovarian xenograft model with lower systemic toxicities by intratumoral delivery (2010)

As successful chemotherapy with the taxanes needs to reduce the toxic side effects against normal tissues and avoid the detrimental effects caused by intolerable solvents, drug delivery system using soluble polymeric micelles tends to be the focus. Docetaxel (Doc) has demonstrated extraordinary activities against a variety of solid tumors. However, the clinical efficacy is contrasted by its toxicity profile. To reduce the toxicity and enhance the circulation time of Doc, core-shell structure nanoparticles were prepared from block copolymer of methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL). It was found that Doc can be incorporated into the nanoparticles with high encapsulation efficiency of more than 90%. In vitro release study showed that Doc was released from Doc-np in a sustained manner. In vitro cytotoxicity studies indicated that IC50 of docetaxel-loaded nanoparticles (Doc-np) against SKOV3 cells is significantly lower than that of free Doc. Furthermore, intratumoral administration was applied to improve the tumor-targeted delivery in the in vivo evaluation. Compared with free Doc, Doc-np exhibited superior antitumor effect by delaying tumor growth when delivered intratumorally. Blood test, as well as liver and kidney function, showed that Doc-np had little toxicity while free Doc induce severe anemia and liver damage. These results suggest that Doc-np are effective in inhibiting the growth of human ovarian cancer with little toxicity to normal tissues, and intratumoral delivery of Doc-np could be a clinically useful therapeutic regimen and merit more research to evaluate the feasibility of clinical application.
Insulin Delivery with Plasmid DNA (1999)

Success in controlling hyperglycemia in type I diabetics will require a restoration of basal insulin. To this end, three plasmid DNAs (pDNA) encoding preproinsulin were compared for constitutive expression and processing to insulin in nonendocrine cells in vitro. The pDNAs were designed to express rat proinsulin I (VR-3501), rat proinsulin I with the B10 aspartic acid point mutation (VR-3502), and a derivative of VR-3502 with a furin cleavage site added at the B-chain and C-peptide junction (VR-3503). Cells transfected with VR-3501 or VR-3502 were able to secrete only proinsulin, whereas transfection with VR-3503 yielded 30-70% mature insulin, which could be increased to >99% by cotransfection with a furin expression plasmid (VR-3505). The insulin produced was biologically active. The bilateral injection of 100 microg of VR-3502 plasmid into the tibialis anterior muscles of mice on two consecutive days yielded, on average, several hundred picograms of heterologous proinsulin per milliliter of serum. In BALB/c mice, serum proinsulin peaked 7-14 days postinjection and declined to preinjection levels by days 21-28. In athymic nude mice, serum proinsulin was sustained for at least 6 weeks. The therapeutic efficacy of delivering insulin via muscle injection of pDNA was evaluated in athymic nude mice made diabetic with the beta cell toxin streptozotocin (STZ). All animals given control DNA died within 1 week of receiving STZ while 40% of the mice coinjected with plasmids VR-3503 and VR-3505 lived through the duration of the 4-week experiment. Muscles of the surviving animals contained 17-100 ng of immune-reactive insulin (IRI), 86-94% of which was mature insulin. The results suggest that heterologous insulin made in muscle increased the survival rate. We propose that insulin plasmid expression in skeletal muscle may be a valid approach to basal insulin delivery. The feasibility of plasmid DNA-based delivery of basal insulin was investigated. An expression system consisting of pDNAs encoding a selectively mutated rat preproinsulin and mouse furin was developed and characterized in vitro and in vivo. When injected with preproinsulin pDNA, the mouse tibialis anterior muscle expressed and released proinsulin into serum at levels comparable to normal basal insulin in rodents. These heterologous proinsulin levels were sustained for several weeks in immune-compromised nondiabetic mice. Mouse muscle coinjected with a pDNA encoding the endopeptidase furin and a pDNA encoding a pre-proinsulin modified to contain two furin cleavage sites produced fully processed insulin. This muscle-made insulin appears to have contributed to the survival of mice treated with a highly diabetogenic dose of streptozotocin, a beta cell toxin. The results demonstrate that skeletal muscle is able to express and deliver therapeutic insulin from plasmid DNA.
The chemoattractant activity of rheumatoid synovial fluid for human lymphocytes is due to multiple cytokines (1996)

The majority of synovial fluids from 29 rheumatoid arthritis patients were strongly attractive for normal blood lymphocytes judged by assays of polarization and collagen gel invasion. While rheumatoid synovial fluids contained IL-15, IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) at levels sufficient to attract lymphocytes, inhibition of the activity of any single cytokine using specific antibody did not abolish the activity of the fluid. However combinations of anti-cytokine antibodies used together (anti-IL-15+anti-MCP-1; anti-IL-8+anti-MCP-1 or +anti-MIP-1 alpha) inhibited most of the activity, suggesting that attraction of lymphocytes by the fluids is due to a combination of attractants. Blood lymphocytes required activation by overnight culture to respond optimally, while rheumatoid synovial tissue lymphocytes responded to synovial fluids without a requirement for a period of culture. Lymphocytes derived from rheumatoid synovial fluids were poorly responsive to locomotor stimulants. Most of the responding cells from blood mononuclear cell fractions were T lymphocytes of the CD45RO isotype. Incubation in the presence of cyclosporin A or corticosteroids inhibited the response of lymphocytes to the fluids, but the presence of non-steroidal anti-inflammatory drugs (NSAIDs) and other agents used in therapy of the patients from whom the fluids were taken had no inhibitory effect.
Identification of androgen-responsive microRNAs and androgen-related genes in breast cancer. (2013)

Our findings indicated that the recruitment of IQWD1 to ARs may be a prerequisite for the growth stimulation by androgens through ARs in breast cancer cells.
OX40 Controls Functionally Different T Cell Subsets and Their Resistance to Depletion Therapy (2007)

T cell depletion is a widely used approach in clinical transplantation. However, not all T cells are equally sensitive to depletion therapies and a significant fraction of T cells persists even after aggressive treatment. The functional attributes of such T cells and the mechanisms responsible for their resistance to depletion are poorly studied. In the present study, we showed that CD4(+) T cells that are resistant to polyclonal anti-lymphocyte serum (ALS) mediated depletion exhibit phenotypic features of memory cells and uniformly express OX40 on the cell surface. Studies using the foxp3gfp knockin mice revealed that the remaining CD4(+)OX40(+) cells consist of Foxp3(+) Tregs and Foxp3(-) T effector/memory cells. The ALS-resistant CD4(+)OX40(+) cells failed to mediate skin allograft rejection upon adoptive transferring into congenic Rag(-/-) mice, but removal of Foxp3(+) Tregs from the OX40(+) cells resulted in prompt skin allograft rejection. Importantly, OX40 is critical to survival of both Foxp3(+) Tregs and T effector/memory cells. However, OX40 exhibits opposing effects on the functional status of Foxp3(+) Tregs and T effector/memory cells, as stimulation of OX40 on T effector cells induced amplified cell proliferation but stimulation of OX40 on the Foxp3(+) Tregs impaired their suppressor functions. Our study demonstrates that OX40 is a critical molecule in regulating survival and functions of depletion-resistant T cells; and these findings may have important clinical implications.
Use of Bacille Calmette–Guerin (BCG) in multiple sclerosis (1999)

We studied the effect of Bacille Calmette-Guerin (BCG) vaccine as an immunomodulator in MS. According to the guidelines for clinical trials in MS, a single crossover, MRI-monitored trial was performed in 14 patients with relapsing-remitting MS. After treatment, MRI activity was significantly reduced. No major adverse effects were reported. Adjuvant therapy with BCG vaccine was safe and merits study in MS.
Donepezil for dementia with Lewy bodies: A randomized, placebo‐controlled trial (2012)

Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated.
Anti-CXCR4 Monoclonal Antibodies Recognizing Overlapping Epitopes Differ Significantly in Their Ability To Inhibit Entry of Human Immunodeficiency Virus Type 1 (2005)

CXCR4 is one of two physiologically relevant human immunodeficiency type 1 (HIV-1) entry coreceptors. Studies of CXCR4 mutants have not clearly identified the determinants of coreceptor function and specificity. We therefore used a panel of monoclonal antibodies to further elucidate CXCR4 expression, structure, and function. Our findings show the existence of conformational subpopulations of CXCR4 that are in equilibrium on the cell surface but are not cell type specific as previously reported. HIV-1 X4 isolates can interact with multiple CXCR4 conformations in order to gain entry into target cells.
The Role of Airway Dendritic Cell Populations in Regulation of T-Cell Responses to Inhaled Antigens: Atopic Asthma as a Paradigm (2002)

Chronic atopic asthma in adulthood represents the end stage of a disease process that is initiated during the perinatal period, when the naive immune system is first confronted with potentially allergenic airborne antigens. The initial phase involves compartmentalization of immunological memory into either the T-helper (Th)-1 or Th2 cytokine phenotypes, in atopic and nonatopics, respectively, and in a subset of atopics, this results in chronic Th2 cytokine-driven inflammation in the airways. Dendritic cells appear to play a key role in directing the memory generation process, and in subsequently controlling the intensity and duration of the ensuing Th-cell responses responsible for this inflammation.
Rethinking Rapid Response Teams (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Surface Plasmon Resonance (SPR) Analysis of Binding Interactions of Proteins in Inner-Ear Sensory Epithelia (2008)

Surface plasmon resonance is an optical technique utilized for detecting molecular interactions. Binding of a mobile molecule (analyte) to a molecule immobilized on a thin metal film (ligand) changes the refractive index of the film. The angle of extinction of light, reflected after polarized light impinges upon the film, is altered, monitored as a change in detector position for the dip in reflected intensity (the surface plasmon resonance phenomenon). Because the method strictly detects mass, there is no need to label the interacting components, thus eliminating possible changes of their molecular properties. We have utilized surface plasmon resonance to study the interaction of proteins of hair cells.
Mechanically Durable Carbon Nanotube−Composite Hierarchical Structures with Superhydrophobicity, Self-Cleaning, and Low-Drag (2009)

Superhydrophobic surfaces with high contact angle and low contact angle hysteresis exhibit a self-cleaning effect and low drag for fluid flow. The lotus (Nelumbo nucifera) leaf is one of the examples found in nature for superhydrophobic surfaces. For the development of superhydrophobic surfaces, which is important for various applications such as glass windows, solar panels, and microchannels, materials and fabrication methods need to be explored to provide mechanically durable surfaces. It is necessary to perform durability studies on these surfaces. Carbon nanotube (CNT), composite structures which would lead to superhydrophobicity, self-cleaning, and low-drag, were prepared using a spray method. As a benchmark, structured surfaces with lotus wax were also prepared to compare with the durability of CNT composite structures. To compare the durability of the various fabricated surfaces, waterfall/jet tests were conducted to determine the loss of superhydrophobicity by changing the flow time and pressure conditions. Wear and friction studies were also performed using an atomic force microscope (AFM) and a ball-on-flat tribometer. The changes in the morphology of the structured surfaces were examined by AFM and optical imaging. We find that superhydrophobic CNT composite structures showed good mechanical durability, superior to the structured surfaces with lotus wax, and may be suitable for real world applications.
Analysis of the electrical excitation of CNS neurons (1998)

The artificial excitation process of neurons of the central nervous system depends on the applied extracellular field, on the geometry of the neuron and on the electrical properties of the neural subunits. Results of computer simulations are based on a compartment model of the neuron and its equivalent electrical network. Furthermore, a theory is presented which generalizes the activating function concept known from peripheral nerve stimulation. The theory predicts the influence of electrical and geometrical parameters on the excitation threshold. Generally, the myelinated axon is the part of a neuron which is most excitable to a given applied field. An example demonstrates that for a target neuron the quotient (anodic threshold current)/(cathodic threshold current) essentially depends on the position and orientation of the neuron relative to the electrode.
Organohalide lead perovskites for photovoltaic applications (2014)

This review presents the state-of-the-art organohalide lead perovskites, which are currently making an immense impact across the photovoltaic community.
Induction of Apoptosis by Apo-2 Ligand, a New Member of the Tumor Necrosis Factor Cytokine Family (1996)

Cytokines in the tumor necrosis factor (TNF) family regulate development and function of the immune system. We have isolated a new member of this family, designated Apo-2 ligand (Apo-2L), via an expressed sequence tag. Apo-2L is a 281-amino acid protein, related most closely to Fas/Apo-1 ligand. Transfected Apo-2L is expressed at the cell surface with its C terminus exposed, indicating a type II transmembrane protein topology. Like Fas/Apo-1 ligand and TNF, the C-terminal extracellular region of Apo-2L (amino acids 114-281) exhibits a homotrimeric subunit structure. Soluble Apo-2L induces extensive apoptosis in lymphoid as well as non-lymphoid tumor cell lines. The effect of Apo-2L is not inhibited by soluble Fas/Apo-1 and TNF receptors; moreover, expression of human Fas/Apo-1 in mouse fibroblasts, which confers sensitivity to induction of apoptosis by agonistic anti-Fas/Apo-1 antibody, does not confer sensitivity to Apo-2L. Hence, Apo-2L acts via a receptor which is distinct from Fas/Apo-1 and TNF receptors. These results suggest that, along with other family members such as Fas/Apo-1 ligand and TNF, Apo-2L may serve as an extracellular signal that triggers programmed cell death.
TNF-α Increases Expression of IL-6 and ICAM-1 Genes Through Activation of NF-κB in Osteoblast-like ROS17/2.8 Cells (1998)

Tumor necrosis factor-alpha (TNF-alpha) plays a key role in inflammatory diseases such as rheumatoid arthritis and in postmenopausal osteoporosis. In various tissues, TNF-alpha action is mediated by a transcription factor, nuclear factor-kappa B (NF-kappaB). However, little is known about how TNF-alpha exerts its action in osteoblasts. We thus examined the effect of TNF-alpha on the activation of NF-kappaB in rat osteoblast-like osteosarcoma cells (ROS17/2.8). Electrophoretic mobility shift assay revealed that the activation of the p50-p65 heterodimer NF-kappaB was induced by TNF-alpha as early as 15 minutes followed by a persistent activation for 48 h. When the binding activity of NF-kappaB in cytosol was examined using detergents that dissociate NF-kappaB from an inhibitory protein IkappaB, it decreased during the initial 30 minutes and then increased to the unstimulated level. Northern blot analysis revealed a marked increase in the mRNA levels of p105, a precursor of p50, 6 h after TNF-alpha and a gradual increase in p65 mRNA levels during the initial 1 h. Significant increase in both mRNA levels continued until 24 h after TNF-alpha. These results suggest that the rapid activation of NF-kappaB by TNF-alpha is mainly due to the nuclear translocation of NF-kappaB pre-existing in cytosol, and that the subsequent increase in the expression of p50 and p65 may result in the persistent activation of NF-kappaB during TNF-alpha stimulation. TNF-alpha also increased the mRNA levels of interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1). An antioxidant, N-acetyl-L-cysteine, significantly attenuated the TNF-alpha-dependent increase in these mRNAs, and simultaneously reduced the activation of NF-kappaB by TNF-alpha, indicating that NF-kappaB mediates the TNF-alpha-dependent expression of IL-6 and ICAM-1 in ROS17/2.8 cells. These results suggest that the activation of NF-kappaB by TNF-alpha may play an important role in the production of cytokines and cell adhesion molecules from osteoblasts, leading to the promotion of bone resorption and inflammation.
Antimicrobial Peptides from Plants (2015)

Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms.
DIFFERENCES IN ENZYME CONTENT OF AZUROPHIL AND SPECIFIC GRANULES OF POLYMORPHONUCLEAR LEUKOCYTES (1968)

In the previous paper we presented findings which indicated that enzyme heterogeneity exists among PMN leukocyte granules. From histochemical staining of bone marrow smears, we obtained evidence that azurophil and specific granules differ in their enzyme content. Moreover, a given enzyme appeared to be restricted to one of the two types. Clear results were obtained with alkaline phosphatase, but those with a number of other enzymes were suggestive rather than conclusive. Since the approach used previously was indirect, it was of interest to localize the enzymes directly in the granules. Toward this end, we carried out cytochemical procedures for five enzymes on normal rabbit bone marrow cells which had been fixed and incubated in suspension. The localization of reaction product in the granules was determined by electron microscopy. In accordance with the results obtained on smears, azurophil granules were found to contain peroxidase and three lysosomal enzymes: acid phosphatase, arylsulfatase, and 5'-nucleotidase; specific granules were found to contain alkaline phosphate. Specific granules also contained small amounts of phosphatasic activity at acid pH. Another finding was that enzyme activity could not be demonstrated in mature granules with metal salt methods (all except peroxidase); reaction product was seen only in immature granules. The findings confirm and extend those obtained previously, indicating that azurophil granules correspond to lysosomes whereas specific granules represent a different secretory product.