gebhart/patrepeval huggingface dataset:
CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice (2015)

The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised "3KO" mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic "FCGR2A" mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG "Fc" effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases.
Preparations of Melatonin and 1-Hydroxymelatonin, and Its Novel Nucleophilic Dimerization to (±)-3a,3a'-Bispyrrolo[2,3-b]indoles (1999)

A unique synthetic method for melatonin was established through biologically promising synthetic intermediates.1-Hydroxymelatonin was prepared as crystals for the first time.It reacted with 85% formic acid to give (?)-3a,3a'-bispyrrolo[2,3-b]indole compound, whose structure was unequivocally determined by X-Ray crystallographic analysis.We have disclosed that in an acidic conditions 1-hydroxyindoles2 (A) undergo five types of reactions, as shown in Scheme 1, such as 1) regioselective nuclwphilic substitution to give 5-substituted indoles ( ~) , 32) formation of kabutanes ( ~) , 3 e 3) dimerization to afford 52'-hisindole derivatives ( D ) , ~~ 4) formation of pyrrolo[2,3-blindoles (E and ~) , 3 a and 5) dehydroxylation to give indoles ( ~) , 3 depending on acids and the structure of 1-hydroxyindoles.In our continuing research on verifying 1-hydroxyindole hypotheses,4 we have now reached to the stage to clarify the reactivity of 1-hydroxymelatonin (1).When it reacts with acid, departure of its 1-hydroxy group as a water would form a stable cation (2) (Scheme 2).Then, what happens?We have expected to discover a new type of nuclwphilic substitution reaction through 2.To answer the above question, we needed biologically important melatonin5 (3) as a starting material.Although we have reported four-step melatonin synthesis6 from tryptamine (4) as shown in Scheme 2 through Nb-acetyltryptamine (Ja), Q and 74 both nuclwphilic substitution and dehydroxylation took place in the fourth step of the treatment of 7a with BFyMeOH culminating in the formation of about 20:l mixture of 3 and 5a in 85% yield.The problem is that Rf values of them are close and their separations are not easy particularly in large scale production.Therefore, we tried to find another improved synthesis for 3 Scheme 1 1-Hydroxyindoles R , R', R" = an appropriate substiuent Nucleophilic
Triethylene-Tetramine(Trien) Therapy for Wilson's Disease. (1991)

Triethylene tetramine (trien), in increasing dose from 1.0-2.0 g/day to 2.5-3.0 g/day, was used for 4 Japanese patients with Wilson's disease who were intolerant of D-penicillamine (D-PC). Before the treatment, urinary copper excretion (UCE) was 70-96 micrograms/day. UCE increased to 1,512-2,352 micrograms/day on the day of initial administration, and remained at levels between 350-1,100 micrograms/day, thereafter. During 2 months of trien therapy, neurological deficits regressed in three patients, and only slightly in one patient. No adverse effects were observed. These results and the retrospective survey on 17 patients treated with D-PC confirmed that trien is less potent but a safer copper chelating agent than D-PC. The transient aggravation of neurological deficits seen in two patients during the early stage of the treatment suggested that trien, as D-PC, should be started in small doses and gradually increased.
Interactive Medical Image Segmentation Using Snake and Multiscale Curve Editing (2013)

Image segmentation is typically applied to locate objects and boundaries, and it is an essential process that supports medical diagnosis, surgical planning, and treatments in medical applications. Generally, this process is done by clinicians manually, which may be accurate but tedious and very time consuming. To facilitate the process, numerous interactive segmentation methods have been proposed that allow the user to intervene in the process of segmentation by incorporating prior knowledge, validating results and correcting errors. The accurate segmentation results can potentially be obtained by such user-interactive process. In this work, we propose a novel framework of interactive medical image segmentation for clinical applications, which combines digital curves and the active contour model to obtain promising results. It allows clinicians to quickly revise or improve contours by simple mouse actions. Meanwhile, the snake model becomes feasible and practical in clinical applications. Experimental results demonstrate the effectiveness of the proposed method for medical images in clinical applications.
Varicella-zoster virus: isolation and propagation in human melanoma cells at 36 and 32 degrees C (1978)

Cell lines derived from human malignant melanoma tumors are susceptible to infection with varicella-zoster virus (VZV). Within 5 days after inoculation of vesicular fluid, cytopathic changes appeared in melanoma cell monolayer cultures that were incubated at either 36 or 32 degrees C. The VZV isolates at the two temperatures were serially propagated by passage of trypsin-dispersed infected cells. A plaque assay was developed utilizing melanoma cell monolayers overlaid with nutrient medium containing carboxymethylcellulose. By this assay method, the growth cycle of a VZV isolate propagated at 36 degrees C was studied and compared with that of another VZV isolate grown at 32 degrees C. With equivalent infected-cell inocula at a ratio on one inoculum cell to eight uninfected cells, the yield of cell-free virus at an incubation temperature of 32 degrees C was slightly higher than at 36 degrees C, although the peak occurred 60 h, rather than 36 h, postinfection. It was also found that the titer of low-passage VZV propagated at 36 degrees C was 0.5 to 1 log higher when assayed at 32 degrees C rather than at 36 degrees C.
En Passant Mutagenesis: A Two Step Markerless Red Recombination System (2010)

Bacterial artificial chromosomes are used to maintain and modify large sequences of different origins in Escherichia coli. In addition to RecA-based shuttle mutagenesis, Red recombination is commonly used for sequence modification. Since foreign sequences, such as antibiotic resistance genes as well as frt- or loxP-sites are often unwanted in mutant BAC clones, we developed a Red-based technique that allows for the scarless generation of point mutations, deletions, and insertion of smaller and larger sequences. The method employs a sequence duplication that is inserted into the target sequence in the first recombination step and the excision of the selection marker by in vivo I-SceI cleavage and the second Red recombination. To allow for convenient and highly efficient mutagenesis without the use of additional plasmids, the E. coli strain GS1783 with a chromosomal encoded inducible Red- and I-SceI-expression was created.
BET Bromodomain as a Target of Epigenetic Therapy (2016)

Acetylation of histone is a key epigenetic modification, and contributes to many DNA-dependent cellular processes. The bromodomain structure, which consists of approximately 110 amino acid residues, serves as a 'reader' that recognizes acetylated lysine in histones, leading to recruitment of positive transcriptional elongation factor b (P-TEFb), and thereby promoting transcriptional activity and chromatin remodeling. Among bromodomain-containing proteins, members of the bromodomain and extra-terminal domain (BET) family contain tandem N-terminal bromodomains. BET proteins, especially BRD4, have attracted interest as candidate therapeutic targets due to their putative involvement in the pathogenesis of various diseases, including cancer and inflammatory diseases. Several BET inhibitors are under clinical trial for treatment of various cancers. Furthermore, polypharmacological agents such as dual kinase/BET inhibitors and dual histone deacetylase (HDAC)/BET inhibitors have recently been developed, in addition to agents that degrade BET family proteins, such as proteolysis-targeting chimeras (PROTACs). This paper reviews recent progress in epigenetic therapy targeting the BET bromodomain.
Lipid Peroxidation and Antioxidant Defence System in Patients with Active or Inactive Behçet's Disease (2003)

To evaluate plasma lipid peroxidation and enzymatic and non-enzymatic antioxidant systems in patients with Behçet's disease, plasma malondialdehyde levels and total antioxidant status, erythrocyte superoxide dismutase and whole blood glutathione peroxidase activities were studied in 15 patients with active disease and in 30 with inactive disease, and compared with 20 age-matched healthy control subjects. Plasma malondialdehyde levels were significantly higher in patients with active Behçet's disease than in patients with inactive disease, who had significantly higher levels than control subjects. The plasma total antioxidant status of both groups of patients was significantly lower than that of controls. Furthermore, whole blood glutathione peroxidase activity was significantly lower in patients with active versus inactive Behçet's disease. There were no significant differences in erythrocyte superoxide dismutase levels between the groups. In conclusion, there is an increase in oxidative stress in Behçet's disease. Despite this stress, the antioxidant system is deficient and inadequate, especially in patients who are in an active phase of the disease.
Serial noninvasive photoacoustic imaging of neovascularization in tumor angiogenesis (2005)

We present photoacoustic images of tumor neovascularization obtained over a 10-day period after subcutaneous inoculation of pancreatic tumor cells in a rat. The images were obtained from ultrasound generated by absorption in hemoglobin of short laser pulses at a wavelength of 1064 nm. The ultrasound signals were measured in reflection mode using a single scanning piezodetector, and images were reconstructed with a weighted delay-and-sum algorithm. Three-dimensional data visualize the development and quantify the extent of individual blood vessels around the growing tumor, blood concentration changes inside the tumor and growth in depth of the neovascularized region.
Inhibition of IL-10 Production by Maternal Antibodies against Group B Streptococcus GAPDH Confers Immunity to Offspring by Favoring Neutrophil Recruitment (2011)

Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, septicemia, and meningitis. We have previously shown that in adult mice GBS glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extracellular virulence factor that induces production of the immunosuppressive cytokine interleukin-10 (IL-10) by the host early upon bacterial infection. Here, we investigate whether immunity to neonatal GBS infection could be achieved through maternal vaccination against bacterial GAPDH. Female BALB/c mice were immunized with rGAPDH and the progeny was infected with a lethal inoculum of GBS strains. Neonatal mice born from mothers immunized with rGAPDH were protected against infection with GBS strains, including the ST-17 highly virulent clone. A similar protective effect was observed in newborns passively immunized with anti-rGAPDH IgG antibodies, or F(ab')(2) fragments, indicating that protection achieved with rGAPDH vaccination is independent of opsonophagocytic killing of bacteria. Protection against lethal GBS infection through rGAPDH maternal vaccination was due to neutralization of IL-10 production soon after infection. Consequently, IL-10 deficient (IL-10(-/-)) mice pups were as resistant to GBS infection as pups born from vaccinated mothers. We observed that protection was correlated with increased neutrophil trafficking to infected organs. Thus, anti-rGAPDH or anti-IL-10R treatment of mice pups before GBS infection resulted in increased neutrophil numbers and lower bacterial load in infected organs, as compared to newborn mice treated with the respective control antibodies. We showed that mothers immunized with rGAPDH produce neutralizing antibodies that are sufficient to decrease IL-10 production and induce neutrophil recruitment into infected tissues in newborn mice. These results uncover a novel mechanism for GBS virulence in a neonatal host that could be neutralized by vaccination or immunotherapy. As GBS GAPDH is a structurally conserved enzyme that is metabolically essential for bacterial growth in media containing glucose as the sole carbon source (i.e., the blood), this protein constitutes a powerful candidate for the development of a human vaccine against this pathogen.
Ischemic kidney injury and mechanisms of tissue repair (2010)

Acute kidney injury (AKI) may result from ischemia or by the use of nephrotoxic agents. The incidence of AKI is variable, depends on comorbidities, and ranges from 5 to 35% in all hospitalized patients. The mechanisms of kidney injury exist within a large network of signaling pathways driven by interplay of inflammatory cytokines/chemokines, reactive oxygen species (ROS), and apoptotic factors. The effects and progression of injury overlap extensively with the remarkable ability of the kidney to repair itself both by intrinsic and extrinsic mechanisms that involve specific cell receptors/ligands as well as possible paracrine influences. The fact that kidney injury is usually part of a generalized comorbid condition makes it all the more challenging in terms of assessment of severity. In this review, we attempt to analyze the mechanisms of ischemic injury and repair in acute and chronic kidney disease from the perspectives of both preclinical and human studies.
Targeted delivery of antineoplastic agent to bone: biodistribution studies of technetium-99m-labeled gem-bisphosphonate conjugate of methotrexate. (1996)

The present study indicates that the concept of treating osteosarcoma or metastatic tumors of bone with this class of agents has a firm basis.
Overexpression of the Wilms' tumor gene WT1 in esophageal cancer. (2004)

These results may indicate an important role of the WT1 gene in the tumorigenesis of ESCC.
Insufficient TLR Activation Contributes to the Slow Development of CD8+ T Cell Responses in Trypanosoma cruzi Infection (2009)

During experimental infection with Trypanosoma cruzi, mice develop a strong CD8(+) T cell response focused mainly on a few immunodominant peptides encoded in trans-sialidase family genes. Despite the potency of this response, the initial emergence and peak of parasite-specific CD8(+) T cells has been noted to be relatively slow. In this study, we further document this delayed onset of T cell responses to T. cruzi as measured by the increase in frequency of parasite-specific T cells, the effector function of these cells, T cell proliferation in general, and the recruitment of cells into the draining lymph nodes. This delay does not appear to be the result of general immunosuppressive effects of the infection, a limitation in parasite numbers, or parasite trafficking to lymph nodes or to the specific epitope. Increasing the initial infecting dose or the density of parasite epitopes on APCs can modestly speed the generation of anti-T. cruzi T cell responses. Given these characteristics of the response, we propose that T. cruzi is a stealth invader, largely avoiding recognition by components of the innate immune system until the infection is well established. This conclusion is supported by the ability to accelerate the induction of T cell responses to T. cruzi by administration of ligands for TLR2 and TLR9 at the time of infection. These studies highlight a previously unappreciated mechanism of immune evasion, the surreptitious establishment of infection, by the protozoan T. cruzi.
MAGE-A gene expression pattern in primary breast cancer. (2001)

Melanoma antigen (MAGE)-A-derived peptides elicit a strong in vitro T-cell response against tumor cells. For determination of MAGE-A1, -2, -3, -4, -6, and -12 expression profile in invasive breast cancer, we developed a multiplex seminested reverse transcription-PCR-method. In total, 18 of 67 (27%) tumors were positive for at least one of these MAGE transcripts, and the expression pattern was heterogeneous: MAGE-A1 was positive in 4 of 67 (6%), MAGE-A2 in 13 of 67 (19%), MAGE-A3 in 7 of 67 (10%), MAGE-A4 in 9 of 67 (13%), MAGE-A6 in 10 of 67 (15%), and MAGE-A12 in 6 of 67 (9%) patients. The MAGE-A transcripts were more frequently expressed in ductal breast carcinomas compared with other histomorphological types. We observed a preferential expression of MAGE-A in patients at a higher risk of recurrence: those harboring tumors with high levels of the protease urokinase-type plasminogen activator and its inhibitor plasminogen activator inhibitor 1, high score of the Ki-67 proliferation antigen, and lesser degree of differentiation. Our findings suggests a potential involvement of MAGE-A in tumor progression, with potential implications for active immunotherapy.
Chemokine Upregulation Follows Cytokine Expression in Chronic Relapsing Experimental Autoimmune Encephalomyelitis (2003)

Chronic relapsing experimental autoimmune encephalomyelitis (ChREAE) is an autoimmune disease of the central nervous system (CNS) induced by CNS myelin components. In the early active stage, both ChREAE and multiple sclerosis (MS) are characterized by the presence of perivascular inflammatory cuffs disseminated in the CNS. There is growing evidence that chemoattractant cytokines (chemokines) play an important role in this process. The main goal of the present study was to analyse the hypothesis that chemokine expression in the CNS during autoimmune inflammation is regulated by proinflammatory cytokines. To address this concept, we analysed temporal relations between chemokine and cytokine expression during ChREAE. Phasic upregulation of gene expression for chemokines T-cell activation gene 3 (TCA-3)/CCL1, monocyte chemoattractant protein-1 (MCP-1)/CCL2, macrophage inflammatory protein-1 alpha (MIP-1alpha)/CCL3, MIP-1beta/CCL4, regulated on activation normal T cell expressed and secreted (RANTES)/CCL5 and MIP-2/CXCL2-3 as well as cytokines tumour necrosis factor-alpha (TNF-alpha), -beta, LT-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) in the CNS was observed during attacks of ChREAE. Expression of cytokines TNF-beta and LT-beta preceded, and the expression of TGF-beta1 followed chemokine upregulation. Our results suggest that chemokine expression during CNS autoimmune inflammation may be regulated by some proinflammatory cytokines.
Protein Synthesis, Posttranslational Modifications, and Aginga (1992)

Posttranslational modifications of proteins are involved in determining their activities, stability, and specificity of interaction. More than 140 major and minor modifications of proteins have been reported. Of these, only a few have been studied in relation to the aging of cells, tissues, and organisms. These include phosphorylation, methylation, ADP-ribosylation, oxidation, glycation, and deamidation. Several of these modifications occur on proteins involved in crucial cellular processes, such as DNA synthesis, protein synthesis, protein degradation, signal transduction, cytoskeletal organization, and the components of extracellular matrix. Some of the modifications are the markers of abnormal and altered proteins for rapid degradation. Others make them less susceptible to degradation by normal proteolytic enzymes, and hence these accumulate during aging.
A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps. (1993)

A recently described splice variant of CD44 expressed in metastasizing cell lines of rat tumors has been shown to confer metastatic potential to a non-metastasizing rat pancreatic carcinoma cell line and to non-metastasizing sarcoma cells. Homologues of this variant as well as several other CD44 splice variants are also expressed at the RNA level in human carcinoma cell lines from lung, breast, and colon, and in immortalized keratinocytes. Using antibodies raised against a bacterial fusion protein encoded by variant CD44 sequences, we studied the expression of variant CD44 glycoproteins in normal human tissues and in colorectal neoplasia. Expression of CD44 variant proteins in normal human tissues was readily found on several epithelial tissues including the squamous epithelia of the epidermis, tonsils, and pharynx, and the glandular epithelium of the pancreatic ducts, but was largely absent from other epithelia and from most non-epithelial cells and tissues. In human colorectal neoplasia CD44 variant proteins, including homologues of those which confer metastatic ability to rat tumors, were found on all invasive carcinomas and carcinoma metastases. Interestingly, focal expression was also observed in adenomatous polyps, expression being related to areas of dysplasia. The distribution of the CD44 variants in human tissues suggests that they play a role in a few restricted differentiation pathways and that in colorectal tumors one of these pathways has been reactivated. The finding that metastasis-related variants are already expressed at a relatively early stage in colorectal carcinogenesis and tumor progression, i.e., in adenomatous polyps, suggests the existence of a yet unknown selective advantage linked to CD44 variant expression. The continued expression in metastases would be compatible with a role in the metastatic process.