gebhart/patrepeval huggingface dataset:
T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. (1982)

Culturing BALB/c B cells for 6 d at low cell density in the presence of lipopolysaccharide (LPS) results in the appearance of a small number of IgG plaque-forming cells (PFC). The addition of supernatants from concanavalin A (Con A)-induced alloreactive (AKR anti-B6) long-term T cell lines (PK 7.1.1a and 7.1.2) or a T cell hybridoma (FS7-6.18) to LPS-treated B cells resulted in a marked increase in IgG PFC (3--10-fold higher than in cultures treated with LPS alone. The number of induced IgG PFC was not affected by removing IgG-bearing cells on the fluorescence-activated cell sorter, indicating that T cell-derived B cell differentiation factor enhances isotype switching of sIgG- cells, rather than selecting and expanding pre-existing subpopulations of sIgG+ cells. We also investigated the subclass of IgG produced in the absence or presence of T cell factors and found that PK 7.1.1a, PK 7.1.2, and FS7-6.18 supernatants selectively increased IgG1 production. Several other T cell supernatants containing a variety of lymphokines had no effect, suggesting that PK 7.1.1a, PK 7.1.2, and FS7-6.18 lines produce factor(s) that can specifically enhance the recovery of IgG secreting cells in culture in the presence of LPS. These factors, which we have termed B cell differentiation factors, are different from interleukin 1, interleukin 2, T cell-replacing factor, colony-stimulating factor, macrophage-activating factor, and immune interferon. Our results suggest that soluble factors produced by T cell lines and hybridomas can markedly influence both the class and subclass of Ig produced by B cells.
Tumor-Specific Methylation in Saliva: A Promising Biomarker for Early Detection of Head and Neck Cancer Recurrence (2007)

Gene methylation in saliva is a promising biomarker for the follow-up and early detection of still curable relapses of head and neck squamous cell carcinoma patients.
Retinal Damage by Visible Light (1968)

SEVERE damage to the retina by exposure to light has recently been demonstrated by Noell 1,2 and by us. 3,4 To establish the pathogenetic mechanisms, a series of electron microscopic studies of the retinas which had been exposed to lights under several conditions has been in progress in this laboratory. Depending on the duration of the light exposure and the nature of the light sources, the retinas show damage varying all the way from total degeneration of the whole retina to minimal changes in the photoreceptors. Upon exposure to relatively cold light at a brightness of approximately 750 foot-candles (ft-c), photoreceptic outer segments of the albino rat demonstrate remarkable membranous changes. The purpose of this paper is to describe such changes in the photoreceptic cells and to discuss the mechanisms of the damage. Materials and Methods Albino rats were mainly used in the experiment. Ordinary wire mesh animal cages
CD28 blockade controls T cell activation to prevent graft-versus-host disease in primates (2018)

Controlling graft-versus-host disease (GVHD) remains a major unmet need in stem cell transplantation, and new, targeted therapies are being actively developed. CD28-CD80/86 costimulation blockade represents a promising strategy, but targeting CD80/CD86 with CTLA4-Ig may be associated with undesired blockade of coinhibitory pathways. In contrast, targeted blockade of CD28 exclusively inhibits T cell costimulation and may more potently prevent GVHD. Here, we investigated FR104, an antagonistic CD28-specific pegylated-Fab', in the nonhuman primate (NHP) GVHD model and completed a multiparameter interrogation comparing it with CTLA4-Ig, with and without sirolimus, including clinical, histopathologic, flow cytometric, and transcriptomic analyses. We document that FR104 monoprophylaxis and combined prophylaxis with FR104/sirolimus led to enhanced control of effector T cell proliferation and activation compared with the use of CTLA4-Ig or CTLA4-Ig/sirolimus. Importantly, FR104/sirolimus did not lead to a beneficial impact on Treg reconstitution or homeostasis, consistent with control of conventional T cell activation and IL-2 production needed to support Tregs. While FR104/sirolimus had a salutary effect on GVHD-free survival, overall survival was not improved, due to death in the absence of GVHD in several FR104/sirolimus recipients in the setting of sepsis and a paralyzed INF-γ response. These results therefore suggest that effectively deploying CD28 in the clinic will require close scrutiny of both the benefits and risks of extensively abrogating conventional T cell activation after transplant.
Adipose Tissue Dysfunction in Nascent Metabolic Syndrome (2013)

The metabolic syndrome (MetS) confers an increased risk for both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome's low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT) in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin) and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin), as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.
In situ Expression of Cytokines and Cellular Adhesion Molecules in the Skin of Patients with Systemic Sclerosis (1993)

Cytokines and cellular adhesion molecules (CAMs) may play a role in the inflammatory and fibrotic processes underlying systemic sclerosis (SSc). We compared the immunohistological distribution of cytokines and CAMs in skin biopsies from 12 SSc patients and 14 normal (NL) individuals. Among CAMs, vascular cell adhesion molecule-1 (VCAM-1), which mediates leukocyte-endothelial adhesion, showed increased expression on SSc versus NL endothelium and stratum granulosum. P-selectin was up-regulated in SSc versus NL stratum granulosum. The CD44 lymphocyte homing receptor showed the most striking differences between SSc and NL: its expression was increased in SSc stratum granulosum, stratum spinosum, on lymphocytes, and macrophages. Regarding cytokines, interleukin-6 (IL-6) expression was increased on SSc versus NL endothelium and fibroblasts. Tumor necrosis factor-alpha (TNF-alpha) reactivity was more prevalent in SSc than NL stratum granulosum, whereas IL-8 expression was higher on SSc compared to NL endothelium. Some CAMs, such as VCAM-1 and P-selectin, and cytokines, namely TNF-alpha and IL-8, were more commonly found in skin biopsies taken from early (< or = 1 year's duration) SSc, while others, such as IL-6, showed up-regulation in the late stage of the disease. The results suggest that certain CAMs and cytokines may play a differential role in both the early, inflammatory, and the late, fibrotic stage of SSc.
High performance membranes based on ionic liquid polymers for CO2 separation from the flue gas (2012)

Three vinyl functionalized imidazolium based room-temperature ionic liquids (RTILs): 1-vinyl-3-ethylimidazolium dicyanamide ([veim][dca]), 1-vinyl-3-butylimidazolium dicyanamide ([vbim][dca]) and 1-vinyl-3-heptylimidazolium dicyanamide ([vhim][dca]) were synthesized and UV-polymerized to form free standing membranes. The pure gas permeabilities of CO2 and N2 of these newly developed membranes acquired at 1 atm 35 °C increased with an increase in the number of N-alkyl group in the monomers but their ideal CO2–N2 selectivities decreased. The three vinyl functionalized monomers were blended with three free RTILs: 1-ethyl-3-methylimidazolium dicyanamide ([emim][dca]), 1-ethyl-3-methylimidazolium tetracyanoborate ([emim][B(CN)4]) and 1-ethyl-3-methylimidazolium tetrafluoroborate ([emim][BF4]) and subsequently subjected to UV-polymerization to form the poly(RTIL)–RTIL composite membranes. The incorporation of free RTILs not only significantly increases the CO2 permeability but also greatly improves the CO2–N2 selectivity. The best separation performance is achieved for the poly([vbim][dca])–[emim][B(CN)4] (1 : 2) and poly([vbim][dca])–[emim][dca] (1 : 2) composite membranes, which have CO2 permeabilities of 340 and 273 barrers and CO2–N2 selectivities of 42 and 53, respectively, at 1 atm 35 °C. The mixed gas permeabilities of these two composite membranes are 297 and 253.5 barrers with corresponding CO2–N2 selectivities of 38.8 and 50.6, respectively, using a 50 : 50 CO2–N2 mixed gas at 2 atm 35 °C. These two composite membranes have separation performance very close to the 2008 “Robeson Upper Bound”, suggesting their potential for industrial applications, especially for the post-combustion flue gas treatment.
COMPARATIVE EVALUATION OF CHELATING AGENTS ON THE MOBILIZATION OF CADMIUM: A MECHANISTIC APPROACH (1996)

A comparative evaluation of chelating agents, namely, diethyl dithiocarbamate (DDC), dimethyl dithiocarbamate (DMDC), 1,4,8,11-tetraazacyclotetradecane (CYCLAM), 1,4,8,12-tetraazacyclopentadecane (TACPD), 2,3-dimercaptosuccinic acid (DMSA), and 2,3-dimercapto-1-propane sulfonate (DMPS) was conducted to assess their efficacy against acute cadmium (Cd) toxicity. DMSA and DMPS appeared to be most effective in reducing mortality as well as Cd burden of liver, kidneys, and brain in cadmium intoxicated mice. DMDC reduced Cd levels only in liver and kidneys, while DDC significantly enhanced its level in brain. CYCLAM and TACPD significantly increased the Cd level in liver and kidneys and were ineffective in brain. The therapeutic index as well as therapeutic efficacy was highest for DMSA followed by DMPS and DMDC. A fair degree of correlation was found to exist between (1) stability constant of Cd chelates and percent survival (r = .438, (2) stability constant and percent transport (r = .479), and (3) percent survival and percent transport (r =.447). However, the lipophilicity did not show any appreciable correlation with percent survival and stability constant of Cd chelates.
Identification of Promiscuous KIF20A Long Peptides Bearing Both CD4+ and CD8+ T-cell Epitopes: KIF20A-Specific CD4+ T-cell Immunity in Patients with Malignant Tumor (2013)

These are the first results showing the presence of KIF20A-specific TH1 cell responses in HNMT patients and underline the possible utility of KIF20A-LPs for propagation of TH1 cells and CTLs.
Modulation of Heterochromatin Protein 1 Dynamics in Primary Mammalian Cells (2003)

Heterochromatin protein 1 (HP1beta), a key component of condensed DNA, is strongly implicated in gene silencing and centromeric cohesion. Heterochromatin has been considered a static structure, stabilizing crucial aspects of nuclear organization and prohibiting access to transcription factors. We demonstrate here, by fluorescence recovery after photobleaching, that a green fluorescent protein-HP1beta fusion protein is highly mobile within both the euchromatin and heterochromatin of ex vivo resting murine T cells. Moreover, T cell activation greatly increased this mobility, indicating that such a process may facilitate (hetero)chromatin remodeling and permit access of epigenetic modifiers and transcription factors to the many genes that are consequently derepressed.
Restored expression of the tumor suppressor gene RUNX3 reduces cancer stem cells in hepatocellular carcinoma by suppressing Jagged1-Notch signaling (2011)

Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene that is downregulated in various cancers. In the present study, we analyzed the regulatory function of RUNX3 on Jagged-1 (JAG1) expression and cancer stem cell (CSC) signaling in hepatocellular carcinoma (HCC). Eleven HCC cell lines and 30 human HCC tissues were used. RUNX3 and JAG1 expression levels were analyzed by immunoblotting and immunohistochemistry. Ectopic RUNX3 expression was induced by introducing RUNX3 cDNA into the RUNX3-negative HCC cell line Hep3B and Huh7 cells. Furthermore endogenous RUNX3 expression was knocked down by RUNX3 siRNA in SK-Hep-1 cells. In order to analyze JAG1 transcriptional regulation, we conducted reporter assays, chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSAs). Tumorigenicity was analyzed using a SCID mouse liver injection model. An inverse correlation was observed between RUNX3 expression and JAG1 expression in most HCC cell lines and tissues. Restoring RUNX3 expression decreased the expression of JAG1 in Hep3B and Huh7 cells, whereas JAG1 expression was upregulated in RUNX3 siRNA-treated SK-Hep-1 cells. Reporter assays, ChIP assays and EMSAs revealed that RUNX3 directly bound to the transcriptional regulatory region of JAG1 and suppressed JAG1 transcription. Moreover, RUNX3 restoration downregulated CSCs by suppressing JAG1-mediated Notch signaling. The tumorigenic capacity of RUNX3-expressing Hep3B cells was lower compared to that of control Hep3B cells. RUNX3 expression suppressed JAG1 expression and resulted in downregulation of tumorigenesis by suppression of JAG1-mediated CSCs.
Association of interleukin‐1 gene polymorphisms with gastric cancer: A meta‐analysis (2006)

Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric cancer by systematically reviewing the risk of the original studies. Thirty-nine studies, which included 6,863 gastric cancer cases and 8,434 controls, met the inclusion criteria and were included in the meta-analysis. By pooling all the studies identified, the summary odds ratio (OR) of gastric cancer risk associated with IL-1B-511T, -31C, +3954T and IL-1RN*2 was 1.26 (95% confidence interval (CI): 1.03-1.55), 1.00 (95% CI: 0.82-1.22), 1.37 (95% CI: 0.94-2.00) and 1.20 (95% CI: 1.01-1.41), respectively. A stratified analysis showed that IL-1B-511T was associated with an increased risk of gastric cancer (intestinal type) (OR = 1.76, 95% CI: 1.12-2.57). Moreover, IL-1RN*2 was also associated with an increased risk of gastric cancer among Caucasians (OR = 1.30, 95% CI: 1.09-1.54). In conclusion, IL-1B-511 and IL-1RN genetic polymorphisms are associated with an increased risk of developing gastric cancer.
Drug evaluation: BG-12, an immunomodulatory dimethylfumarate. (2007)

Biogen Idec Inc, following its acquisition of Fumapharm AG, is developing BG-12 (Panaclar, BG-00012, FAG-201), an oral second-generation fumarate derivative, for the potential treatment of multiple sclerosis (MS). In January 2007, a phase III program for relapsing-remitting MS patients was initiated. The company was also developing the drug for psoriasis and, in October 2003, Biogen Idec expected to commence phase III trials for psoriasis in the US in the following year. In April 2005, the drug met its European phase III psoriasis trial endpoint, with the data expected to be used to support a market authorization filing in Germany in 2005. It was later disclosed that while an application had been filed, this was subsequently withdrawn based on a joint decision by Fumapharm and Biogen Idec. No further development has been reported on BG-12 for psoriasis in the US and it was not listed as a pursued indication on Biogen Idec's April 2007 pipeline.
Hypersensitivity pneumonitis: a comprehensive review. (2001)

Hypersensitivity pneumonitis is a dynamic and heterogeneous group of diseases resulting from inhalational exposure to a variety of organic and inorganic dusts. In the United States, it has predominantly been considered an occupational disease, such as in farmer's lung, bagassosis, and in the plastics and paint industry with isocyanate exposure. In Japan, however, the most common exposure to antigen has been associated with the home environment. All susceptible patient populations are at potential risk to develop this disease under appropriate antigen exposure. The clinical course can be acute, subacute, or chronic depending on the nature of the antigen and the circumstances under which exposure occurs. If unrecognized, any stage of disease has the potential to progress to endstage pulmonary fibrosis. Proper antigen identification and avoidance requires that the physician be keenly aware of its existence and the importance of the detailed occupational and home environmental history. Without a high degree of suspicion, this disease can be easily overlooked and misdiagnosed as another type of inflammatory lung disease. Although the immunologic mechanisms mediating this illness are complex and poorly understood, strict avoidance of the provocative antigen is required for optimal long-term outcome.
Induction of Systemic TH1-Like Innate Immunity in Normal Volunteers Following Subcutaneous but Not Intravenous Administration of CPG 7909, a Synthetic B-Class CpG Oligodeoxynucleotide TLR9 Agonist (2004)

Subcutaneous injection of normal human volunteers with a B-class CpG oligodeoxynucleotide (ODN) TLR9 agonist, CPG 7909, induced a TH1-like pattern of systemic innate immune activation manifested by expression of IL-6, IL-12p40, IFN-alpha, and IFN-inducible chemokines. Serum IP-10 was found to be the most sensitive assay for subcutaneous CPG 7909 stimulation; its level was significantly increased in all subjects at all dose levels, including the lowest tested dose of just 0.0025 mg/kg. This pattern of chemokine and cytokine induction was markedly different from that previously reported to be induced by TLR9 stimulation in rodents, most likely reflecting species-specific differences in the cell types expressing TLR9. Subcutaneous CPG 7909 injection induced transient shifts in blood neutrophils, lymphocytes, and monocytes, consistent with the increased chemokine expression. Levels of acute phase reactants such as C-reactive protein were also increased. A second subcutaneous CPG 7909 injection administered 2 weeks after the first elicited similar immune responses, showing little or no tolerance to the effects of repeated in vivo TLR9 stimulation. Subjects developed dose-dependent transient injection site reactions and flu-like symptoms but otherwise tolerated injection well, with no evidence of organ toxicity or systemic autoimmunity. The activation of innate immunity was dependent on the route of ODN administration, since intravenous injection caused no such effects. These studies indicate that in vivo activation of TLR9 by subcutaneous administration of CPG 7909 could be a well-tolerated immunotherapeutic approach for induction of TH1 innate immune activation.
Signaling through focal adhesion kinase (1997)

Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase implicated in controlling cellular responses to the engagement of cell-surface integrins, including cell spreading and migration, survival and proliferation. Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins, including v-Src. Progress toward elucidating the events leading to FAK activation following integrin-mediated cell adhesion, as well as events downstream of FAK, has come through the identification of FAK phosphorylation sites and interacting proteins. A signaling partnership is formed between FAK and Src-family kinases, leading to tyrosine phosphorylation of FAK and associated 'docking' proteins Cas and paxillin. Subsequent recruitment of proteins containing Src homology 2 domains, including Grb2 and c-Crk, to the complex is likely to trigger adhesion-induced cellular responses, including changes to the actin cytoskeleton and activation of the Ras-MAP kinase pathway.
Prognostic value of glucose transporter 1 expression in patients with hypopharyngeal carcinoma. (2003)

Glut1 expression is an indicator for predicting the prognosis of hypopharyngeal carcinoma.
Safety and immunogenicity of a live oral bivalent typhoid fever (Salmonella typhi Ty21a)-cholera (Vibrio cholerae CVD 103-HgR) vaccine in healthy adults (1995)

The safety and immunogenicity of the live oral attenuated vaccine strains vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a were evaluated alone or in a combined bivalent formulation in four groups composed of 185 healthy European adults. All presentations were well tolerated. The serum anti-S. typhi lipopolysaccharide immunoglobulin G and immunoglobulin A antibody responses were comparable for all groups (66 to 72% seroconversion). The serum vibriocidal antibody seroconversion rate ranged from 78 to 92.5% (P > 0.05) among the groups. However, the peak and geometric mean vibriocidal antibody titers were significantly higher (P < 0.005) in the groups which received the bivalent formulation along with two doses of Ty21a than in the group which received CVD 103-HgR followed by two doses of killed Escherichia coli K-12 placebo. The ingestion of a placebo shortly after CVD 103-HgR may have suppressed the magnitude of the immune response. These findings demonstrate the feasibility of producing multivalent live oral attenuated vaccines.
Human Signal-Regulatory Protein Is Expressed on Normal, But Not on Subsets of Leukemic Myeloid Cells and Mediates Cellular Adhesion Involving Its Counterreceptor CD47 (1999)

Signal-regulatory proteins (SIRPs) comprise a novel transmembrane glycoprotein family involved in the negative regulation of receptor tyrosine kinase-coupled signaling pathways. To analyze the expression and function of SIRPs, we prepared soluble recombinant fusion proteins of the extracellular regions of SIRPalpha1 and SIRPalpha2, as well as a variety of monoclonal antibodies (MoAbs) against these domains. The antibodies reacted predominantly with monocytes, granulocytes, dendritic cells, and their precursors, as well as with bone marrow CD34(+), AC133(+), CD90(+) hematopoietic stem/progenitor cells. In contrast, SIRP expression was absent or significantly reduced on the majority of myeloid blasts from patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML). Functional studies showed that the extracellular domains of SIRPalpha1 and SIRPalpha2 support adhesion of a number of primary hematopoietic cells and cell lines. This interaction could be blocked by 4 of 7 SIRPalpha1-reactive MoAbs. In addition, SIRPalpha1 and SIRPalpha2 competed for the same cell binding site, suggesting a common widely expressed SIRP ligand. In an approach to identify this molecule, MoAbs were generated against the SIRP-binding cell line CCRF-CEM, and MoAb CC2C6 was selected because of its capacity to inhibit cell binding to SIRPalpha1. Further analysis showed that this antibody recognized CD47, a ubiquitously expressed plasma membrane protein previously implicated in integrin function, host defense action, and neutrophil migration. In this study, we identify CD47 as the extracellular ligand for human SIRP and show that these two counterreceptors are involved in cellular adhesion.