gebhart/patrepeval huggingface dataset:
Effects of 1,2-naphthoquinones on human tumor cell growth and lack of cross-resistance with other anticancer agents (1998)

The sensitivity of human tumor and rat prostate tumor cells to a series of naphthoquinones, including tricyclic compounds of the beta-lapachone and dunnione families as well as 4-alkoxy-1,2-naphthoquinones, was evaluated. To better understand the mechanism of cytotoxicity of 1,2-naphthoquinones, the roles of various resistance mechanisms including P-glycoprotein, multidrug resistant associated protein, glutathione (GSH) and related enzymes, altered topoisomerase activity, and overexpression of genes that control apoptosis (bcl-2 and bc-xL) were studied. MCF7 cells were most sensitive to the naphthoquinones with IC50 values ranging from 1.1 to 10.8 microM, as compared to 2.5 to >32 microM for HT29 human colon, A549 human lung, CEM leukemia and AT3.1 rat prostate cancer cells. MCF7 ADR cells, selected for resistance to adriamycin (ADR), displayed cross-resistance to the tricyclic 1,2-naphthoquinones. Drug efflux via a P-glycoprotein mechanism was ruled out as a mechanism of resistance to 1,2-naphthoquinones, since KB-V1 cells expressing high levels of P-glycoprotein and the KB-3.1 parent line were equally sensitive to these compounds. Any resistance of the tricyclic naphthoquinones noted in ADR-resistant cells appeared to relate to the GSH redox cycle and could be circumvented by exposure to buthionine sulfoximine or by changing the structure from a tricyclic derivative to a 4-alkoxy-1,2-naphthoquinone. The 1,2-naphthoquinones were found to be cytotoxic against CEM/VM-1 and CEM/M70-B1 cells that were selected for resistance to teniposide or merbarone, respectively. In addition, cells overexpressing bcl-2 or bcl-xL proteins were as sensitive to 1,2-naphthoquinones as were control cells. Because of their effectiveness in drug-resistant cells, these agents appear to hold promise as effective chemotherapeutic agents.
Fabrication of metallic electrodes with nanometer separation by electromigration (1999)

A simple yet highly reproducible method to fabricate metallic electrodes with nanometer separation is presented. The fabrication is achieved by passing a large electrical current through a gold nanowire defined by electron-beam lithography and shadow evaporation. The current flow causes the electromigration of gold atoms and the eventual breakage of the nanowire. The breaking process yields two stable metallic electrodes separated by ∼1 nm with high efficiency. These electrodes are ideally suited for electron-transport studies of chemically synthesized nanostructures, and their utility is demonstrated here by fabricating single-electron transistors based on colloidal cadmium selenide nanocrystals.
The significance of immunohistochemistry in the diagnosis and therapy of neoplasms (2002)

This review article details the diagnostical significance of immunohistochemistry, which has developed during the last quarter of the century. Certainly, the advancement of monoclonal antibody technology has been of great significance in assuring the place of immunohistochemistry in the modern accurate microscopic diagnosis of human neoplasms, as a method of choice in histopathology. The fact still remains that in order to properly assess any immunohistochemical reactivity used for differential diagnostic purposes, the target cells have to be identified as neoplastically transformed cells by routine histopathological techniques. Selected groups of target molecules of great significance in cancer biology are discussed. The discovery of neoplasm-associated antigens has not only made the more accurate diagnosis of human cancer feasible but has also shed light on the extensive immunophenotypical heterogeneity of even the most closely linked human malignancies. The identification of disseminated neoplastically transformed cells by immunohistochemistry has allowed for a clearer picture of cancer invasion and metastasis, as well as the evolution of the tumour cell associated immunophenotype towards increased malignancy. Some possibilities of neoplasm-associated antigen targeted, receptor-directed immunotherapy are discussed and reviewed in this manuscript. Future antineoplastic therapeutical approaches should see the inclusion of a variety of immunotherapies, in the form of an individualised 'cocktail' specific for the particular immunophenotypical pattern associated with each individual patient's neoplastic disease.
Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin (1993)

Human hemoglobin (Hb) and Hb cross-linked between the alpha subunits with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) were used to treat hemorrhagic shock in water-deprived swine. Water was withheld for 48 h to induce a 10% loss of body mass, and 25 ml/kg of blood were removed in 1 h to produce circulatory shock. Swine were resuscitated with 1) Hb, 2) alpha alpha Hb, 3) human serum albumin, or 4) Ringer lactate. Mild high-output renal failure was observed in the non-cross-linked Hb-treated animals but not in other groups of animals. Swine treated with Hb and alpha alpha Hb had increases in plasma creatine kinase and lactate dehydrogenase activity that were resolved within 7 days. Both Hb- and alpha alpha Hb-treated swine displayed marked elevations of mean blood pressure in the systemic (39 +/- 6 Torr) and pulmonary (20 +/- 6 Torr) circulations that continued for 3 h and were associated with reduced cardiac output and a doubling of the systemic and pulmonary vascular resistances. Oxygen delivery was equivalent, and the rate of correction of the lactic acidosis was equal in all groups.
Molecular Immunologic Strategies to Identify Antigens and B-Cell Responses Unique to Multiple Sclerosis (2001)

Identification of the causative agent of multiple sclerosis (MS) has long eluded investigators and has become the "Holy Grail" of researchers in the field. The immune response in cerebrospinal fluid of patients with MS, indicated by an increased IgG level and the presence of specific oligoclonal bands after electrophoresis, strongly parallels that found in various infectious diseases of the central nervous system. To understand the nature of B-lymphocyte activation in MS, 4 laboratories studied the antigen-binding regions of antibodies found in MS brain demyelinative plaques and cerebrospinal fluid. Each analysis revealed (1) limited germline expression, results not expected for a random bystander response; (2) features consistent with a specific antigen-targeted process; and (3) the clonal expansion of populations of B lymphocytes in MS. The screening of libraries expressing protein products derived from chronic MS plaque messenger RNA with antibodies purified from plaques, cerebrospinal fluid, or serum of patients with MS has thus far not revealed the antigenic target(s) of the MS antibody response. Because putative MS antigens could be in low abundance, the screening of large libraries of random peptides expressed on phage surfaces might offer an alternative approach to identify peptide sequences recognized by MS antibodies. New sophisticated molecular immunologic techniques described herein should enhance our ability to identify putative antigen(s) targets in MS.
The augmentation of in vitro and in vivo tumor-specific T cell-mediated immunity by amplifier T lymphocytes. (1980)

Abstract The present study investigates the role of helper (amplifier) T cells in causing enhanced induction of syngeneic tumor immunity. 2,4,6-Trinitrophenyl- (TNP) reactive helper (amplifier) T cell activity was generated in BALB/c mice by immunization with TNP-isologous mouse γ-globulin after inoculation with TNP conjugates of the nonimmunogenic co-polymer of D-glutamic acid and D-lysine (D-GL). Immunization of these mice with TNP-conjugated syngeneic LSTRA tumor cells led to augmented generation of tumor-specific in vitro cytotoxic T cell activity against LSTRA when compared with the degree of cytotoxicity generated in control mice not primed with TNP. In vivo tumor-neutralizing activity was also augmented in the mice in which TNP-reactive amplifier T cells had been generated before immunization with TNP-LSTRA. Spleen cells from these mice exhibited complete tumor neutralization in a Winn assay. In contrast, spleen cells from mice not primed with TNP before immunization with TNP-LSTRA failed to neutralize viable LSTRA tumor cells, exhibiting only a delay in the appearance of the tumor. The magnitude of tumor-neutralizing activity developed in the presence of TNP-amplifier system was as much as 20-fold greater than for control, and this augmented tumor-neutralizing activity was also tumor specific and T cell mediated. Thus, the present system provides an effective manipulation for eliciting enhanced in vivo tumor rejection as well as in vitro cytotoxic response, and illustrates a role of amplifier T cells in augmentation of syngeneic tumor immunity.
Overexpression of EIF3S3 promotes cancer cell growth (2006)

The results suggest that EIF3S3 regulates cell growth and viability, and that overexpression of the gene may provide growth advantage to the cancer cells.
Cbfa1 Is a Positive Regulatory Factor in Chondrocyte Maturation (2000)

Cbfa1 is a transcription factor that belongs to the runt domain gene family. Cbfa1-deficient mice showed a complete lack of bone formation due to the maturational arrest of osteoblasts, demonstrating that Cbfa1 is an essential factor for osteoblast differentiation. Further, chondrocyte maturation was severely disturbed in Cbfa1-deficient mice. In this study, we examined the possibility that Cbfa1 is also involved in the regulation of chondrocyte differentiation. mRNAs for both Cbfa1 isotypes, type I Cbfa1 (Pebp2alphaA/Cbfa1) and type II Cbfa1 (Osf2/Cbfa1 or til-1), which are different in N-terminal domain, were expressed in terminal hypertrophic chondrocytes as well as osteoblasts. In addition, mRNA for type I Cbfa1 was expressed in other hypertrophic chondrocytes and prehypertrophic chondropcytes. In a chondrogenic cell line, ATDC5, the expression of type I Cbfa1 was elevated prior to differentiation to the hypertrophic phenotype, which is characterized by type X collagen expression. Treatment with antisense oligonucleotides for type I Cbfa1 severely reduced type X collagen expression in ATDC5 cells. Retrovirally forced expression of either type I or type II Cbfa1 in chick immature chondrocytes induced type X collagen and MMP13 expression, alkaline phosphatase activity, and extensive cartilage-matrix mineralization. These results indicate that Cbfa1 is an important regulatory factor in chondrocyte maturation.
Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model (2000)

Presynaptic denervation is likely to play an important role in the pathophysiology of dyskinesias that develop after levodopa administration to patients with Parkinson's disease. In this study, the thresholds of nigrostriatal damage necessary for the occurrence of parkinsonism and levodopa-induced involuntary movements were compared in squirrel monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animals treated with a regimen of MPTP that caused parkinsonism displayed > or =95% striatal dopamine depletion, 90% reduction of striatal dopamine uptake sites, and 70% nigral neuronal loss. Levodopa administration ameliorated the parkinsonian signs of these monkeys but also induced dyskinesias. A separate group of animals was treated with a milder MPTP regimen that caused 60%-70% striatal dopamine depletion, a 50% decrease in dopamine transporter, and 40% loss of dopaminergic nigral neurons. While these monkeys displayed no behavioral signs of parkinsonism, they all became dyskinetic after levodopa administration. The priming effect of levodopa, that is, the recurrence of dyskinesias in animals previously exposed to the drug, was compared in severely versus mildly lesioned monkeys. When severely injured parkinsonian animals underwent a second cycle of levodopa treatment, they immediately and consistently developed involuntary movements. In contrast, the recurrence of dyskinesias in primed monkeys with a partial nigrostriatal lesion required several levodopa administrations and remained relatively sporadic. The data indicate that moderate nigrostriatal damage which does not induce clinical parkinsonism predisposes to levodopa-induced dyskinesias. Once dyskinesias have been induced, the severity of denervation may enhance the sensitivity to subsequent levodopa exposures.
Optimal Cloning of PCR Fragments by Homologous Recombination in Escherichia coli (2015)

PCR fragments and linear vectors containing overlapping ends are easily assembled into a propagative plasmid by homologous recombination in Escherichia coli. Although this gap-repair cloning approach is straightforward, its existence is virtually unknown to most molecular biologists. To popularize this method, we tested critical parameters influencing the efficiency of PCR fragments cloning into PCR-amplified vectors by homologous recombination in the widely used E. coli strain DH5α. We found that the number of positive colonies after transformation increases with the length of overlap between the PCR fragment and linear vector. For most practical purposes, a 20 bp identity already ensures high-cloning yields. With an insert to vector ratio of 2:1, higher colony forming numbers are obtained when the amount of vector is in the range of 100 to 250 ng. An undesirable cloning background of empty vectors can be minimized during vector PCR amplification by applying a reduced amount of plasmid template or by using primers in which the 5' termini are separated by a large gap. DpnI digestion of the plasmid template after PCR is also effective to decrease the background of negative colonies. We tested these optimized cloning parameters during the assembly of five independent DNA constructs and obtained 94% positive clones out of 100 colonies probed. We further demonstrated the efficient and simultaneous cloning of two PCR fragments into a vector. These results support the idea that homologous recombination in E. coli might be one of the most effective methods for cloning one or two PCR fragments. For its simplicity and high efficiency, we believe that recombinational cloning in E. coli has a great potential to become a routine procedure in most molecular biology-oriented laboratories.
Web-based enterprise management architecture (1998)

This article is a description of the Web-Based Enterprise Management initiative. It discusses both the substance of the initiative itself, in the form of the overall architectural approach implied by WBEM, and the industry context that gave rise to WBEM. The industry context is the current state of management systems and software, standardization efforts, and the actual systems being managed. These provided the major influences in shaping the evolution of the WBEM initiative. The substance of the initiative is provided by the WBEM process and information architectures that support a scalable and heterogeneous management structure. The various aspects of the process architecture are covered, including the object manager, object providers, schema management, and protocols required for communication among the various components of the architecture. An overview of the information architecture is provided in the form of a summary of the Desktop Management Taskforce's Common Information Model schema implemented by WBEM.
All Three WW Domains of Murine Nedd4 Are Involved in the Regulation of Epithelial Sodium Channels by Intracellular Na+ (1999)

The amiloride-sensitive epithelial sodium channel (ENaC) plays a critical role in fluid and electrolyte homeostasis and consists of alpha, beta, and gamma subunits. The carboxyl terminus of each ENaC subunit contains a PPxY motif which is necessary for interaction with the WW domains of the ubiquitin-protein ligase, Nedd4. Disruption of this interaction, as in Liddle's syndrome where mutations delete or alter the PY motif of either the beta or gamma subunits, results in increased ENaC activity. We have recently shown using the whole-cell patch clamp technique that Nedd4 mediates the ubiquitin-dependent down-regulation of Na+ channel activity in response to increased intracellular Na+. In this paper, we demonstrate that WW domains 2 and 3 bind alpha-, beta-, and gamma-ENaC with varying degrees of affinity, whereas WW domain 1 does not bind to any of the subunits. We further show using whole-cell patch clamp techniques that Nedd4-mediated down-regulation of ENaC in mouse mandibular duct cells involves binding of the WW domains of Nedd4 to three distinct sites. We propose that Nedd4-mediated down-regulation of Na+ channels involves the binding of WW domains 2 and 3 to the Na+ channel and of WW domain 1 to an unknown associated protein.
Cytotoxic T‐Cell Clones Isolated from Ovarian Tumour Infiltrating Lymphocytes Recognize Common Determinants on Non‐Ovarian Tumour Clones (1993)

CTL-TIL lines have been developed from tumour infiltrating lymphocytes (TIL) from the ascites of patients with ovarian carcinoma, and used to investigate whether common tumour antigens are expressed on allogeneic ovarian tumours epithelial tumour lines derived from colon and pancreatic carcinoma. Three CTL lines expressed preferential cytolytic activity against autologous tumour cells and against certain allogeneic ovarian tumour cells that shared HLA-A2 molecules. Analysis of the target specificity of these CTL lines indicated that they also lysed human colon and pancreatic tumour lines sharing HLA-A2. CTL-TIL clones isolated from these lines were found to lyse HLA-A2+ ovarian, colon and pancreatic tumours, and to recognize clonally distributed common epitopes on pancreas and colon tumour clones. These results indicate that shared tumour antigens can be found among tumours of common epithelial cell origin. These results indicate a novel class of T-cell-definable tumour antigens recognized by tumour-reactive CTL on human tumours and may be significant for understanding of cellular immunity in ovarian cancer, identification of CTL-defined tumour antigens and future adoptive specific immunotherapeutic approaches in ovarian cancer.
Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie (2004)

Recently, pathological prion protein PrP(Sc), the putative key constituent of infectious agents causing transmissible spongiform encephalopathies (TSEs), was found in muscles of rodents experimentally infected with scrapie and in patients with Creutzfeldt-Jakob disease (CJD). For the assessment of risk scenarios originating from these findings (e.g., alimentary transmission of pathogens associated with bovine spongiform encephalopathy [BSE] and chronic wasting disease [CWD] via tainted beef and game or iatrogenic dissemination of CJD agent through contaminated surgical instruments) more detailed information about the time course of PrP(Sc) accumulation in muscles at preclinical and clinical stages of incubation is needed. Here we show that PrP(Sc) in muscles of hamsters fed with scrapie can be detected prior to the onset of clinical symptoms, but that the bulk of PrP(Sc) was deposited late in clinical disease. Additionally, regarding the question of how muscles become invaded, we report on the intramuscular location of PrP(Sc) and substantial indications for centrifugal spread of infection from spinal motor neurons to myofibers. Our findings in a well-established animal model for TSEs contribute to a better assessment of the risks for public health emanating from “Prions in skeletal muscle” and provide new insights into the pathophysiological spread of TSE agents through the body.
Design, implementation, and performance of a native mode ATM transport layer (2002)

We describe the design, implementation, and performance tuning of a transport layer targeted specifically for ATM networks. The layer has been built from scratch to minimize overhead in the critical path and take advantage of ATM adaptation layer 5 functionality. It provides reliable or unreliable data delivery with feedback or leaky-bucket flow control. These services can be combined to create a customized transport service. Our work is novel in that it is the first end-to-end ATM transport service to provide reliable, flow controlled data transfer. We describe the mechanisms and the operating system support needed to provide these services. A detailed performance measurement allows us to determine the bottlenecks in our system and do tune our implementation. With this tuning, we are able to achieve a user-to-user throughput of 55 Mbps between two 66 MHz Intel 80486 personal computers with Fore Systems' HPA-200 EISA-bus host adaptors. The user-to-user latency for small messages is around 720 /spl mu/s. These figures compare favorably with the performance from far more expensive workstations and validate the correctness of our design choices.
Cell size and nucleoid organization of engineered Escherichia coli cells with a reduced genome (2004)

The minimization of a genome is necessary to identify experimentally the minimal gene set that contains only those genes that are essential and sufficient to sustain a functioning cell. Recent developments in genetic techniques have made it possible to generate bacteria with a markedly reduced genome. We developed a simple system for formation of markerless chromosomal deletions, and constructed and characterized a series of large-scale chromosomal deletion mutants of Escherichia coli that lack between 2.4 and 29.7% of the parental chromosome. Combining deletion mutations changes cell length and width, and the mutant cells with larger deletions were even longer and wider than the parental cells. The nucleoid organization of the mutants is also changed: the nucleoids occur as multiple small nucleoids and are localized peripherally near the envelope. Inhibition of translation causes them to condense into one or two packed nucleoids, suggesting that the coupling of transcription and translation of membrane proteins peripherally localizes chromosomes. Because these phenotypes are similar to those of spherical cells, those may be a consequence of the morphological change. Based on the nucleoid localization observed with these mutants, we discuss the cellular nucleoid dynamics.
Drug-induced apoptosis is not necessarily dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line PC-3. (1995)

The propensity of a cell to undergo apoptosis has been proposed to be a determinant for chemotherapy sensitivity that is not directly dependent on specific drug-target interactions. Androgen-independent prostate cancer is typically refractory to cytotoxic drugs, and we tested whether this is due to a loss of the ability to undergo apoptosis. Exposure of the hormone-insensitive and p53-negative human prostate carcinoma cell line PC-3 to 22 microM cisplatin, 1 microM camptothecin, 10 microM tenoposide, 135 nM vincristine, or 10 microM lovastatin for 72 h caused cell death, internucleosomal DNA fragmentation, and morphological changes typical for apoptosis. One microM cycloheximide prevented anticancer drug-induced apoptosis, whereas high concentration (1 mM) of cycloheximide alone induced apoptosis, indicating that protein synthesis was not needed for these cells to undergo apoptosis. Since cycloheximide affected DNA synthesis and proliferation of PC-3 cells, we tested whether the DNA polymerase inhibitor aphidicolin could also suppress drug-induced apoptosis. In contrast to cycloheximide, aphidicolin inhibited only vincristine-induced apoptosis. Cycloheximide prevented drug-induced changes in cell cycle distribution except for vincristine, while aphidicolin led to an accumulation of cells at the G1-S border independent of the drug used. These data indicate that macromolecular synthesis, active cell cycling, and p53 expression are not required for apoptosis to proceed in this system.