tbuckley/cabot-search huggingface dataset:
Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer.
Authors: A Doyle, W J Martin, K Funa, A Gazdar, D Carney, S E Martin, I Linnoila, F Cuttitta, J Mulshine, P Bunn
Journal: The Journal of Experimental Medicine (1985)

We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A,B,C and beta 2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of HLA-A,B,C and beta 2-microglobulin (beta 2m) antigen expression was demonstrated with both radiobinding assays and indirect immunofluorescence assays. Immunoprecipitation of metabolically labeled cells with antibodies to class I antigens showed most SCLC lines to have synthesized almost no beta 2m and HLA-A,B,C proteins. Northern blot analysis, using human HLA-A,B, and beta 2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and beta 2m mRNA, but both gene products could be induced with interferon treatment of SCLC lines. We conclude that human SCLC, in contrast to other lung cancer types, is characterized by greatly reduced transcription of HLA-A,B,C and beta 2m genes, which suggests the existence of a mechanism for evading the host immune response to the tumor and of an E1a-like product in this type of tumor cell.
Sharing cross-reactive groups of MHC class I improves long-term graft survival
Authors: Yvo W.J. Sijpkens, Ilias I.N. Doxiadis, Johan W. de Fijter, Marko J.K. Mallat, Leendert A. van Es, Peter de Lange, Aeilko H. Zwinderman, Rudi G.J. Westendorp, Folkert J. van Kemenade, Jan-Anthonie Bruijn, Frans H.J. Claas, Leendert C. Paul
Journal: Kidney International (1999)
Patterns of phosphoribosylpyrophosphate and ribose-5-phosphate concentration and generation in fibroblasts from patients with gout and purine overproduction.
Authors: M A Becker
Journal: Journal of Clinical Investigation (1976)

In the majority of patients with gout and excessive uric acid production, underlying enzyme abnormalities have not been identified. In the present study, measurement of both the rate of generation and concentration of phosphoribosylpyrophosphate (PP-ribose-P) and the concentration of ribose-5-phosphate in cultured cells were undertaken to establish a classification of purine overproducers to direct study of additional enzyme defects. Fibroblasts were cultured from 24 individuals assigned to 4 groups: group 1, 5 normal controls; group 2, 5 patients with gout and normal dialy urinary uric acid excretion (gouty controls); group 3, 7 patients with well-defined enzyme abnormalities and excessive urinary acid excretion (4 with hypoxanthine-guanine phosphoribosyltransferase deficiency and 3 with excessive PP-ribose-P synthetase activity); and group 4, 7 patients with gout and excessive uric acid excretion but without grossly abnormal activities of the above enzymes in erythrocyte lysates. In all 14 fibroblast strains from patients showing excessive production of uric acid (groups 3 and 4), rates of purine synthesis de novo and PP-ribose-P concentrations exceeded values for cells from control groups. Cells from group 3 patients with hypoxanthine-guanine phosphoribosyltransferase deficiency showed normal PP-ribose-P generation, while those with excessive PP-ribose-P synthetase activity demonstrated increased generation of this regulatory substrate. All strains from group 3 patients had normal ribose-5-phosphate concentrations. Five cell strains from group 4 patients showed one of the two patterns of abnormalities in these measurements seen in strains from group 3 patients: two resembled hypoxanthine-guanine phosphoribosyltransferase-deficient cells, and three resembled cells with excessive PP-ribose-P synthetase activity. Analyses of erythrocyte enzyme preparations from two of these patients in group 4 have led to identification of a kinetic variant of each enzyme as predicted from the foregoing patterns. Two additional group 4 cell lines that showed increased ribose-5-phosphate concentrations in addition to increased PP-ribose-P concentrations and generation were classified in a separate subgroup, since in the individuals excessive purine synthesis appeared to result from increases ribose-5-phosphate concentration, leading to increased availability of PP-ribose-P. No abnormality in either hypoxanthine-guanine phosphoribosyltransferase or PP-ribose-P synthetase has been found in erythrocyte preparations from one patient so classified.
ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain
Authors: Nancy Beyer, David TR Coulson, Shirley Heggarty, Rivka Ravid, G Brent Irvine, Jan Hellemans, Janet A Johnston
Journal: Molecular Neurodegeneration (2009)

ZnT3 is a membrane Zn(2+ )transporter that is responsible for concentrating Zn(2+ )into neuronal presynaptic vesicles. Zn(2+ )homeostasis in the brain is relevant to Alzheimer's disease (AD) because Zn(2+ )released during neurotransmission may bind to Abeta peptides, accelerating the assembly of Abeta into oligomers which have been shown to impair synaptic function.We quantified ZnT3 mRNA levels in Braak-staged human post mortem (pm) brain tissue from medial temporal gyrus, superior occipital gyrus, superior parietal gyrus, superior frontal gyrus and cerebellum from individuals with AD (n = 28), and matched controls (n = 5) using quantitative real-time PCR. ZnT3 mRNA levels were significantly decreased in all four cortical regions examined in the AD patients, to 45-60% of control levels. This reduction was already apparent at Braak stage 4 in most cortical regions examined. Quantification of neuronal and glial-specific markers in the same samples (neuron-specific enolase, NSE; and glial fibrillary acidic protein, GFAP) indicated that loss of cortical ZnT3 expression was more pronounced, and occurred prior to, significant loss of NSE expression in the tissue. Significant increases in cortical GFAP expression were apparent as the disease progressed. No gene expression changes were observed in the cerebellum, which is relatively spared of AD neuropathology.This first study to quantify ZnT3 mRNA levels in human pm brain tissue from individuals with AD and controls has revealed a significant loss of ZnT3 expression in cortical regions, suggesting that neuronal cells in particular show reduced expression of ZnT3 mRNA in the disease. This suggests that altered neuronal Zn(2+ )handling may be an early event in AD pathogenesis.
Parathyroid Hormone-Related Protein Is an Essential Growth Factor for Human Clear Cell Renal Carcinoma and a Target for the von Hippel-Lindau Tumor Suppressor Gene
Authors: Thierry Massfelder, Herve Lang, Eric Schordan, Veronique Lindner, Sylvie Rothhut, Sandra Welsch, Patricia Simon-Assmann, Mariette Barthelmebs, Didier Jacqmin, Jean-Jacques Helwig
Journal: Cancer Research (2004)

Abstract Clear cell renal carcinoma (CCRC) is responsible for 2% of cancer-related deaths worldwide and is resistant to virtually all therapies, indicating the importance of a search for new therapeutic targets. Parathyroid hormone-related protein (PTHrP) is a polyprotein derived from normal and malignant cells that regulates cell growth. In the current study, we show that blocking PTHrP with antibodies or antagonizing the common parathyroid hormone (PTH)/PTHrP receptor, the PTH1 receptor, dramatically blunts the expansion of human CCRC in vitro by promoting cell death. Importantly, in nude mice, anti-PTHrP antibodies induced complete regression of 70% of the implanted tumors by inducing cell death. In addition, we demonstrate that the von Hippel-Lindau tumor suppressor protein, which functions as a gatekeeper for CCRC, negatively regulates PTHrP expression at the post-transcriptional level. These studies indicate that PTHrP is an essential growth factor for CCRC and is a novel target for the von Hippel-Lindau tumor suppressor protein. Taken together, these results strongly suggest that targeting the PTHrP/PTH1 receptor system may provide a new avenue for the treatment of this aggressive cancer in humans.
Re: Prostate Cancer Susceptibility Locus on Chromosome 1q: a Confirmatory Study
Authors: C.-L. Hsieh, A. H. Wu, L. N. Kolonel, D. W. West, I. Oakley-Girvan, J. Halpern, R. S. Paffenbarger, A. S. Whittemore, R. P. Gallagher, C.-Z. Teh
Journal: JNCI Journal of the National Cancer Institute (1997)
Psoriatic spondyloarthropathy: a long term prospective study.
Authors: J G Hanly, M L Russell, D D Gladman
Journal: Annals of the Rheumatic Diseases (1988)

Fifty two patients with psoriatic spondyloarthropathy were monitored prospectively over a mean of 57 months (range 30-107). A comprehensive protocol was used to assess clinical and radiological features of disease activity and severity. Serial radiographs showed a significant increase in the number of patients with syndesmophyte formation and sacroiliitis. In contrast, there was no significant increase in the number of patients with inflammatory neck pain or stiffness, back pain or stiffness, cervical spine limitation, or sacroiliac tenderness. Similarly, there were no significant changes in any of the direct or indirect measurements of thoracolumbar spine mobility. The presence of HLA-B27 did not appear to influence disease progression. These results suggest that although patients with psoriatic spondyloarthropathy have radiological progression of their disease, this remains clinically silent and does not compromise spinal mobility.
Dynamic contrast enhanced MRI of bone marrow oedema in rheumatoid arthritis
Authors: R Hodgson, A Grainger, P O’Connor, T Barnes, S Connolly, R Moots
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Aims:</h3> The aim of this work was to assess the feasibility of using dynamic contrast enhanced (DCE) MRI of bone marrow oedema, to compare it with conventional marrow oedema scoring systems, and to determine the effects of anti-tumour necrosis factor (TNF)α therapy. <h3>Methods:</h3> The wrist and metacarpophalangeal (MCP) joints of 25 patients with rheumatoid arthritis were studied. A total of 14 were imaged before and 1–2 weeks after anti-TNFα therapy. T2-weighted fat-suppressed images were collected. A dynamic series of 24 3D spoiled gradient-echo images were acquired before, during and after the intravenous administration of gadolinium-based contrast medium. Oedema was scored using the conventional Rheumatoid Arthritis MRI Scoring (RAMRIS) system from T2-weighted images. The relative enhancement rate (RER) was calculated using the dynamic series from oedematous bone, bone adjacent to oedema and from an uninvolved bone. <h3>Results:</h3> A total of 56% of patients showed bone marrow oedema. The RER was significantly increased in and adjacent to areas of marrow oedema. There was a significant reduction in the RER after treatment, but not in the RAMRIS score. <h3>Conclusions:</h3> Dynamic contrast enhanced MRI of bone marrow oedema yields additional information to RAMRIS scoring and may be a more sensitive marker of inflammatory activity and response to treatment.
Comparison of acceptability, skin tolerance, and compliance between handwashing and alcohol-based handrub in ICUs: results of a multicentric study
Authors: Bertrand Souweine, Alexandre Lautrette, Claire Aumeran, Marcel Bénédit, Jean Michel Constantin, Michèle Bonnard, Dominique Guélon, Georges Amat, Bruno Aublet, Richard Bonnet, Ousmane Traoré
Journal: Intensive Care Medicine (2009)
Glycated Hemoglobin in 14,850 Adolescent Blood Donors: A Pilot Screening Program
Authors: M. Odette Gore, Stephen J. Eason, Colby R. Ayers, Aslan Turer, Amit Khera, James A. de Lemos, Darren K. McGuire, Merlyn Sayers
Journal: Diabetes Care (2013)

Substantial attention has been paid to the global epidemic of diabetes among adults, but much less data are available for adolescents. Given the recent endorsement by the American Diabetes Association of glycated hemoglobin (HbA1c) for diabetes screening (1), a pilot HbA1c screening program was implemented in adolescent blood donors by Carter BloodCare, the largest independent blood program in Texas.

HbA1c was measured in 14,850 donors 16–19 years old during school blood drives conducted between 1 September 2011 and 30 April 2012. All donors gave informed consent. The main study measures were the prevalence of HbA1c levels in the prediabetes range (5.7–6.4%; 39–46 mmol/mol) and in the diabetes range (≥6.5%; ≥48 mmol/mol), with further stratification by sex, race/ethnicity, and sociodemographic characteristics.

The cohort included 48.7% girls, 54.7% whites, 3.5% blacks, 24.6% Hispanics, 2.3% Asians, and 15% participants of other/unknown race/ethnicity. Table 1 presents cohort characteristics stratified by HbA1c category. The HbA1c level was above the diabetes threshold in 94 donors (0.6%), and in the prediabetes range in 1,479 donors (10%).

View this table:

Table 1 
Sociodemographic characteristics and selected cardiovascular …
Mechanisms influencing the immunodominance of T cell determinants.
Authors: L Adorini, E Appella, G Doria, Z A Nagy
Journal: The Journal of Experimental Medicine (1988)

The preferential recognition of certain amino acid sequences from foreign protein antigens by T cells is referred to as T cell epitope immunodominance. To determine the mechanisms underlying this phenomenon, we have studied the correlation between the interaction of a series of synthetic peptides encompassing the entire hen egg-white lysozyme (HEL) sequence with class II molecules of the H-2k haplotype, and T cell responsiveness to these peptides. After HEL priming, three immunodominant T cell epitopes were found: two, included in the HEL sequences 51-61 and 112-129, were recognized in association with I-Ak molecules, and one, included in sequence 1-18, in association with I-Ek molecules. Accordingly, these peptides bound to the appropriate class II molecule, as demonstrated by competition for antigen presentation. Several other HEL peptides, although capable of associating with class II molecules, were not immunodominant. The absence of immunodominance has been shown to arise by three different mechanisms: (a) competition by an immunodominant peptide for presentation in vivo, (b) failure to generate the peptide during antigen processing, and (c) an inherently poor capacity of the T cell repertoire to respond to a particular peptide-MHC complex.
The mysterious death of Francesco I de' Medici and Bianca Cappello: an arsenic murder?
Authors: Francesco Mari, Aldo Polettini, Donatella Lippi, Elisabetta Bertol
Journal: BMJ (2006)

Modern analytical techniques have allowed re-evaluation of the cause of death of Francesco I de9 Medici and his wife, Bianca Cappello. It now seems that the grand-ducal couple died of acute arsenic poisoning and not malaria as previously believed
Combination of Tumor Site–Located CTL-Associated Antigen-4 Blockade and Systemic Regulatory T-Cell Depletion Induces Tumor-Destructive Immune Responses
Authors: Sebastian Tuve, Bing-Mae Chen, Ying Liu, Tian-Lu Cheng, Papa Touré, Papa Salif Sow, Qinghua Feng, Nancy Kiviat, Robert Strauss, Shaoheng Ni, Zong-Yi Li, Steve R. Roffler, André Lieber
Journal: Cancer Research (2007)

Abstract Accumulating data indicate that tumor-infiltrating regulatory T cells (Treg) are present in human tumors and locally suppress antitumor immune cells. In this study, we found an increased Treg/CD8 ratio in human breast and cervical cancers. A similar intratumoral lymphocyte pattern was observed in a mouse model for cervical cancer (TC-1 cells). In this model, systemic Treg depletion was inefficient in controlling tumor growth. Furthermore, systemic CTL-associated antigen-4 (CTLA-4) blockade, an approach that can induce tumor immunity in other tumor models, did not result in TC-1 tumor regression but led to spontaneous development of autoimmune hepatitis. We hypothesized that continuous expression of an anti–CTLA-4 antibody localized to the tumor site could overcome Treg-mediated immunosuppression and locally activate tumor-reactive CD8+ cells, without induction of autoimmunity. To test this hypothesis, we created TC-1 cells that secrete a functional anti–CTLA-4 antibody (TC-1/αCTLA-4-γ1 cells). When injected into immunocompetent mice, the growth of TC-1/αCTLA-4-γ1 tumors was delayed compared with control TC-1 cells and accompanied by a reversion of the intratumoral Treg/CD8 ratio due to an increase in tumor-infiltrating IFNγ-producing CD8+ cells. When local anti–CTLA-4 antibody production was combined with Treg inhibition, permanent TC-1 tumor regression and immunity was induced. Importantly, no signs of autoimmunity were detected in mice that received local CTLA-4 blockade alone or in combination with Treg depletion. [Cancer Res 2007;67(12):5929–39]
Podocyte-Specific Deletion of Yes-Associated Protein Causes FSGS and Progressive Renal Failure
Authors: Monica Schwartzman, Antoine Reginensi, Jenny S. Wong, John M. Basgen, Kristin Meliambro, Susanne B. Nicholas, Vivette D'Agati, Helen McNeill, Kirk N. Campbell
Journal: Journal of the American Society of Nephrology (2015)

FSGS is the most common primary glomerular disease underlying ESRD in the United States and is increasing in incidence globally. FSGS results from podocyte injury, yet the mechanistic details of disease pathogenesis remain unclear. This has resulted in an unmet clinical need for cell-specific therapy in the treatment of FSGS and other proteinuric kidney diseases. We previously identified Yes-associated protein (YAP) as a prosurvival signaling molecule, the in vitro silencing of which increases podocyte susceptibility to apoptotic stimulus. YAP is a potent oncogene that is a prominent target for chemotherapeutic drug development. In this study, we tested the hypothesis that podocyte-specific deletion of Yap leads to proteinuric kidney disease through increased podocyte apoptosis. Yap was selectively silenced in podocytes using Cre-mediated recombination controlled by the podocin promoter. Yap silencing in podocytes resulted in podocyte apoptosis, podocyte depletion, proteinuria, and an increase in serum creatinine. Histologically, features characteristic of FSGS, including mesangial sclerosis, podocyte foot process effacement, tubular atrophy, interstitial fibrosis, and casts, were observed. In human primary FSGS, we noted reduced glomerular expression of YAP. Taken together, these results suggest a role for YAP as a physiologic antagonist of podocyte apoptosis, the signaling of which is essential for maintaining the integrity of the glomerular filtration barrier. These data suggest potential nephrotoxicity with strategies directed toward inhibition of YAP function. Further studies should evaluate the role of YAP in proteinuric glomerular disease pathogenesis and its potential utility as a therapeutic target.
MIXED AGGLUTINATION WITH TISSUE SECTIONS
Authors: Olav Tönder, Felix Milgrom, Ernest Witebsky
Journal: The Journal of Experimental Medicine (1964)

The mixed agglutination procedure was applied to tissue sections. Microtome sections of bovine tissue were placed on coverglasses, fixed by acetone or formalin, and incubated with various dilutions of rabbit antisera. The binding of antibodies to the tissue sections was detected by the addition of an indicator system composed of sheep erythrocytes sensitized by subagglutinating doses of the corresponding rabbit antiserum, and agglutinated by goat antiserum to rabbit serum. In positive reactions the indicator cells covered the tissue, whereas in negative tests, the erythrocytes detached and the tissue appeared uncovered. It was demonstrated that the method is capable of detecting both saline-extractable and saline-non-extractable antigens. In addition to species-specific antigens, organ-specific antigens of adrenal and brain were detected. The method was characterized by a very high sensitivity in detecting antibodies. Its possible application as a tool for investigations on tissue antigens and antibodies was discussed.
Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer
Authors: Marie C. Chia, Abby Leung, Tiffany Krushel, Nehad M. Alajez, Kwok W. Lo, Pierre Busson, Henry J. Klamut, Carlo Bastianutto, Fei-Fei Liu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The Epstein Barr virus (EBV) is intimately associated with nasopharyngeal cancer (NPC) in a latent state expressing a limited number of genes. The process of switching from latency to replication is not well understood, particularly in response to DNA stress; hence, the focus of this study is on an EBV-positive NPC model. Experimental Design: C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 μg/mL) assayed subsequently for relative EBV copy number (BamHI) and lytic gene expression (BRLF1 and BZLF1) using quantitative real-time PCR. Chromatin immunoprecipitation was conducted to assess the interaction of the transcription factor nuclear factor-Y (NF-Y) with promoter sequences. Results: Radiation-induced and cisplatin-induced BamHI expression, along with increased levels of BRLF1 and BZLF1 in a dose-dependent and time-dependent manner, associated with the immediate nuclear transactivation of the transcription factor NF-Y and its own increased transcription of NF-Y subunits 8 h posttreatment. In silico analysis revealed three putative NF-Y consensus-binding sequences in the promoter region of BRLF1, which all interacted with NF-Y in response to radiation and cisplatin, confirmed using chromatin immunoprecipitation. Introduction of dominant-negative NF-YA reduced BRLF1 expression after radiation and cisplatin by 2.8-fold; in turn, overexpression of NF-YA resulted in a 2-fold increase in both BRLF1 and BZLF1 expression. Conclusions: These results show that NF-Y is an important mediator of EBV stress response in switching from a latent to lytic state. This novel insight could provide a potential therapeutic strategy to enhance NPC response to radiation and cisplatin.