tbuckley/cabot-search huggingface dataset:
SURFACE TENSION OF SERUM
Authors: P. Lecomte du Noüy
Journal: The Journal of Experimental Medicine (1923)

An attempt was made to apply to the study of immune sera the fact, pointed out in our previous papers, that at a given dilution the serum shows a maximum drop of surface tension in function of time (time-drop). The results of the experiments here reported would seem to indicate that: 1. The time-drop of a serum solution is greater after the animal has been immunized than before immunization (from 50 to 100 per cent). 2. The time-drop is maximum at a dilution of 1:10,000, as had been predicted from the data previously acquired. 3. The size of the molecules or micellæ is probably unchanged after immunization, since the maximum drop is not shifted then. 4. Measurements made during the process of immunization showed that the time-drop increases after the 8th day and second injection, and reaches a maximum toward the 13th day, while the controls undergo no increase. 5. The injection of substances non-productive of antibodies, such as homologous cells or turpentine, does not result in the production of a permanent maximum. This shows that the maximum observed when heterologous cells are used is due to the presence of antibodies, and not to the mere injection of foreign material. 6. The measurement of the refractive index of the sera failed to demonstrate any differences between the sera of the controls and those of the experimental animals.
Dermatology and history in Wales (Cymru)*
Authors: GEOFFREY HODGSON
Journal: British Journal of Dermatology (1974)

The development of dermatology in Wales (Cymru) is traced against a short history of the independent kingdom which became the Principality. Skin diseases were treated by the earliest Cymry, Celtic druids, Celto‐Christian priests, Anglo‐Saxon leeches and court physicians, and later by medieval university graduates and unskilled village herbalists and, when industrialization came, by ‘truck doctors’ and general practitioners. The early dermatologists are described. Traditional holy wells and folk medicine form connecting links.
Human Cytomegalovirus Inhibits Erythropoietin Production
Authors: Lynn M. Butler, Mensur Dzabic, Frank Bakker, Belghis Davoudi, Hannah Jeffery, Piotr Religa, Krzysztof Bojakowski, Koon-Chu Yaiw, Afsar Rahbar, Cecilia Söderberg-Naucler
Journal: Journal of the American Society of Nephrology (2014)

Anemia is a feature of CKD and a complication of renal transplantation, often caused by impaired production of erythropoietin. The kidney is a target organ for human cytomegalovirus (hCMV) in such patients, but it is not known whether hCMV effects erythropoietin production. We found that kidneys from patients with CKD were positive for hCMV protein and that blood levels of hCMV IgG inversely correlated with red blood cell count. In mice, systemic murine cytomegalovirus infection decreased serum erythropoietin levels. In human erythropoietin-producing cells, hCMV inhibited hypoxia-induced expression of erythropoietin mRNA and protein. hCMV early gene expression was responsible, as ultraviolet-inactivated virus had no effect and valganciclovir treatment showed that late gene expression was nonessential. Hypoxia-induced gene transcription is controlled by the transcription factors hypoxia-inducible transcription factor (HIF)-1α and HIF2α, which are constitutively produced but stable only under low oxygen conditions. We found that hCMV inhibited constitutive production of HIF2α mRNA. HIF2α is thought to be the master regulator of erythropoietin transcription. Single-cell analysis revealed that nuclear accumulation of HIF2α was inhibited in hCMV-infected cells, and the extent of inhibition correlated with hCMV protein expression. Our findings suggest that renal hCMV infection could induce or exacerbate anemia in patients.
Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach
Authors: Julio A Freyre-González, José A Alonso-Pavón, Luis G Treviño-Quintanilla, Julio Collado-Vides
Journal: Genome biology (2008)

Abstract Background Previous studies have used different methods in an effort to extract the modular organization of transcriptional regulatory networks. However, these approaches are not natural, as they try to cluster strongly connected genes into a module or locate known pleiotropic transcription factors in lower hierarchical layers. Here, we unravel the transcriptional regulatory network of Escherichia coli by separating it into its key elements, thus revealing its natural organization. We also present a mathematical criterion, based on the topological features of the transcriptional regulatory network, to classify the network elements into one of two possible classes: hierarchical or modular genes. Results We found that modular genes are clustered into physiologically correlated groups validated by a statistical analysis of the enrichment of the functional classes. Hierarchical genes encode transcription factors responsible for coordinating module responses based on general interest signals. Hierarchical elements correlate highly with the previously studied global regulators, suggesting that this could be the first mathematical method to identify global regulators. We identified a new element in transcriptional regulatory networks never described before: intermodular genes. These are structural genes that integrate, at the promoter level, signals coming from different modules, and therefore from different physiological responses. Using the concept of pleiotropy, we have reconstructed the hierarchy of the network and discuss the role of feedforward motifs in shaping the hierarchical backbone of the transcriptional regulatory network. Conclusions This study sheds new light on the design principles underpinning the organization of transcriptional regulatory networks, showing a novel nonpyramidal architecture composed of independent modules globally governed by hierarchical transcription factors, whose responses are integrated by intermodular genes.
ZBRK1 Acts as a Metastatic Suppressor by Directly Regulating <i>MMP9</i> in Cervical Cancer
Authors: Li-Fang Lin, Chih-Hung Chuang, Chien-Feng Li, Ching-Chun Liao, Chun-Pei Cheng, Tian-Lu Cheng, Meng-Ru Shen, Joseph T. Tseng, Wen-Chang Chang, Wen-Hwa Lee, Ju-Ming Wang
Journal: Cancer Research (2009)

Abstract The BRCA1-interacted transcriptional repressor ZBRK1 has been associated with antiangiogenesis, but direct evidence of a tumor suppressor role has been lacking. In this study, we provide evidence of such a role in cervical carcinoma. ZBRK1 levels in cervical tumor cells were significantly lower than in normal cervical epithelial cells. In HeLa cervical cancer cells, enforced expression inhibited malignant growth, invasion, and metastasis in a variety of in vitro and in vivo assays. Expression of the metalloproteinase MMP9, which is known to be an important driver of invasion and metastasis, was found to be inversely correlated with ZBRK1 in tumor tissues and a target for repression in tumor cells. Our findings suggest that ZBRK1 acts to inhibit metastasis of cervical carcinoma, perhaps by modulating MMP9 expression. Cancer Res; 70(1); 192–201
Class I major histocompatibility complex-restricted cytotoxic T lymphocytes specific for Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines against which they were raised.
Authors: A B Hill, S P Lee, J S Haurum, N Murray, Q Y Yao, M Rowe, N Signoret, A B Rickinson, A J McMichael
Journal: The Journal of Experimental Medicine (1995)

We have raised CD8+ cytotoxic T lymphocytes (CTL) from three Epstein-Barr virus-seropositive donors by incubating peripheral blood lymphocytes with irradiated autologous B95.8-strain EBV-transformed B lymphoblastoid cells (LCL). However, to detect lysis in a standard 51Cr release assay of the LCL against which these CTL were raised, superinfection with recombinant vaccinia expressing the appropriate EBV protein or incubation with the peptide epitope was necessary. The untreated LCL were not lysed, even though Western blotting demonstrated that they expressed the EBV antigens containing the CTL epitopes. We have found CTL of this phenotype that are restricted by human leukocyte antigen-A2, -A3, -B7, or -B39, and which recognize the EBV latent proteins, EBV nuclear antigen (EBNA)-3A, EBNA-3C, or terminal protein. During these experiments, we identified a new human leukocyte antigen-A3-restricted EBNA-3A epitope, residues 603-611, RLRAEAGVK. We raised a spontaneous LCL, transformed by endogenous EBV, from one donor, but this was also not lysed. For at least one of the epitopes, CTL from another donor lysed the LCL without superinfection or addition of peptides. We conclude that the CTL were unable to achieve a high enough avidity of interaction with untreated LCL to trigger effector function, although the LCL were able to stimulate them to grow in vitro for up to 4 mo. To assess whether a small percentage of the LCL might possess a higher antigen density, we used an assay of tumor necrosis factor release from a CTL clone, which was able to detect antigen-bearing cells representing only 1% of a stimulating LCL population. Nevertheless, the untreated autologous LCL line failed to stimulate tumor necrosis factor release.
The neuroprotective properties of palmitoylethanolamine against oxidative stress in a neuronal cell line
Authors: R Scott Duncan, Kent D Chapman, Peter Koulen
Journal: Molecular Neurodegeneration (2009)

N-acylethanolamines (NAEs) are lipids upregulated in response to cell and tissue injury and are involved in cytoprotection. Arachidonylethanolamide (AEA) is a well characterized NAE that is an endogenous ligand at cannabinoid and vanilloid receptors, but it exists in small quantities relative to other NAE types. The abundance of other NAE species, such as palmitoylethanolamine (PEA), together with their largely unknown function and receptors, has prompted us to examine the neuroprotective properties and mechanism of action of PEA. We hypothesized that PEA protects HT22 cells from oxidative stress and activates neuroprotective kinase signaling pathways.Indeed PEA protected HT22 cells from oxidative stress in part by mediating an increase in phosphorylated Akt (pAkt) and ERK1/2 immunoreactivity as well as pAkt nuclear translocation. These changes take place within a time frame consistent with neuroprotection. Furthermore, we determined that changes in pAkt immunoreactivity elicited by PEA were not mediated by activation of cannabinoid receptor type 2 (CB2), thus indicating a novel mechanism of action. These results establish a role for PEA as a neuroprotectant against oxidative stress, which occurs in a variety of neurodegenerative diseases.The results from this study reveal that PEA protects HT22 cells from oxidative stress and alters the localization and expression levels of kinases known to be involved in neuroprotection by a novel mechanism. Overall, these results identify PEA as a neuroprotectant with potential as a possible therapeutic agent in neurodegenerative diseases involving oxidative stress.
BNP-Guided Heart Failure Therapy in Older Patients—Reply
Authors: Hans-Peter Brunner La Rocca
Journal: JAMA (2009)

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Protection against tuberculosis: cytokines, T cells, and macrophages
Authors: S H E Kaufmann
Journal: Annals of the Rheumatic Diseases (2002)

Tuberculosis remains a major health problem, with two million deaths and eight million new cases annually. At the same time, two billion people (one third of the total world population) are infected with the aetiological agent, <i>Mycobacterium tuberculosis.</i> Of these, fewer than 10% ever develop disease, although the pathogen is not eradicated but rather contained in discrete lesions. Hence, the immune system is highly effective in containing the pathogen, but fails to eradicate it. Disease typically develops through reactivation once the immune system is weakened. The immune response to <i>M tuberculosis</i> is T cell dependent. It comprises not only the conventional CD4 and CD8 T cells, but also γδ T cells and CD1 restricted T cells. γδ T cells recognise phospholigands and no presentation molecules are known thus far. CD1 restricted T cells recognise glycolipids, which are highly abundant components of the mycobacterial cell wall. Although different T cells are required for optimum protection, the immune mechanisms known to have a role in acquired resistance can be associated with two major mechanisms: (<i>a</i>) activation of macrophages by cytokines; (<i>b</i>) direct cytolytic activity. In vivo granuloma formation, which is central to protection, is induced and sustained by cytokines. Mycobacteria are contained within granulomas and in this way are prevented from spreading all over the body.
Hsp104 antagonizes α-synuclein aggregation and reduces dopaminergic degeneration in a rat model of Parkinson disease
Authors: Christophe Lo Bianco, James Shorter, Etienne Régulier, Hilal Lashuel, Takeshi Iwatsubo, Susan Lindquist, Patrick Aebischer
Journal: Journal of Clinical Investigation (2008)

Parkinson disease (PD) is characterized by dopaminergic neurodegeneration and intracellular inclusions of alpha-synuclein amyloid fibers, which are stable and difficult to dissolve. Whether inclusions are neuroprotective or pathological remains controversial, because prefibrillar oligomers may be more toxic than amyloid inclusions. Thus, whether therapies should target inclusions, preamyloid oligomers, or both is a critically important issue. In yeast, the protein-remodeling factor Hsp104 cooperates with Hsp70 and Hsp40 to dissolve and reactivate aggregated proteins. Metazoans, however, have no Hsp104 ortholog. Here we introduced Hsp104 into a rat PD model. Remarkably, Hsp104 reduced formation of phosphorylated alpha-synuclein inclusions and prevented nigrostriatal dopaminergic neurodegeneration induced by PD-linked alpha-synuclein (A30P). An in vitro assay employing pure proteins revealed that Hsp104 prevented fibrillization of alpha-synuclein and PD-linked variants (A30P, A53T, E46K). Hsp104 coupled ATP hydrolysis to the disassembly of preamyloid oligomers and amyloid fibers composed of alpha-synuclein. Furthermore, the mammalian Hsp70 and Hsp40 chaperones, Hsc70 and Hdj2, enhanced alpha-synuclein fiber disassembly by Hsp104. Hsp104 likely protects dopaminergic neurons by antagonizing toxic alpha-synuclein assemblies and might have therapeutic potential for PD and other neurodegenerative amyloidoses.
Cord-Blood Transplants from Unrelated Donors in Patients with Hurler's Syndrome
Authors: Susan L. Staba, Maria L. Escolar, Michele Poe, Young Kim, Paul L. Martin, Paul Szabolcs, June Allison-Thacker, Susan Wood, David A. Wenger, Pablo Rubinstein, John J. Hopwood, William Krivit, Joanne Kurtzberg
Journal: New England Journal of Medicine (2004)

Hurler's syndrome (the most severe form of mucopolysaccharidosis type I) causes progressive deterioration of the central nervous system and death in childhood. Allogeneic bone marrow transplantation before the age of two years halts disease progression and prolongs life, but many children lack a bone marrow donor. We investigated the feasibility of using cord-blood transplants from unrelated donors and a myeloablative preparative regimen that did not involve total-body irradiation in young children with Hurler's syndrome.Between December 1995 and October 2002, 20 consecutive children with Hurler's syndrome received busulfan, cyclophosphamide, and antithymocyte globulin before receiving cord-blood transplants from unrelated donors. The children were subsequently evaluated for engraftment, adverse effects, and effects on disease symptoms.Cord-blood donors had normal alpha-L-iduronidase activity (mean number of cells, 10.53x10(7) per kilogram of body weight) and were discordant for up to three of six HLA markers. Neutrophil engraftment occurred a median of 24 days after transplantation. Five patients had grade II or grade III acute graft-versus-host disease; none had extensive chronic graft-versus-host disease. Seventeen of the 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral-blood alpha-L-iduronidase activity (event-free survival rate, 85 percent). Transplantation improved neurocognitive performance and decreased somatic features of Hurler's syndrome.Cord blood from unrelated donors appears to be an excellent source of stem cells for transplantation in patients with Hurler's syndrome. Sustained engraftment can be achieved without total-body irradiation. Cord-blood transplantation favorably altered the natural history of Hurler's syndrome and thus may be important to consider in young children with this form of the disease.
Circulating Biomarkers and Abdominal Aortic Aneurysm Incidence
Authors: Aaron R. Folsom, Lu Yao, Alvaro Alonso, Pamela L. Lutsey, Emil Missov, Frank A. Lederle, Christie M. Ballantyne, Weihong Tang
Journal: Circulation (2015)

The pathogenesis of abdominal aortic aneurysm (AAA) is complex. Cross-sectional studies have connected circulating biomarkers with AAA, but prospective evidence is limited.
Intracellular MUC1 Peptides Inhibit Cancer Progression
Authors: Benjamin G. Bitler, Ina Menzl, Carmen L. Huerta, Barbara Sands, Wendy Knowlton, Andrew Chang, Joyce A. Schroeder
Journal: Clinical Cancer Research (2008)

Abstract Purpose: During cancer progression, the oncoprotein MUC1 binds β-catenin while simultaneously inhibiting the degradation of the epidermal growth factor receptor (EGFR), resulting in enhanced transformation and metastasis. The purpose of this study was to design a peptide-based therapy that would block these intracellular protein-protein interactions as a treatment for metastatic breast cancer. Experimental Design: The amino acid residues responsible for these interactions lie in tandem in the cytoplasmic domain of MUC1, and we have targeted this sequence to produce a MUC1 peptide that blocks the protumorigenic functions of MUC1. We designed the MUC1 inhibitory peptide (MIP) to block the intracellular interactions between MUC1/β-catenin and MUC1/EGFR. To allow for cellular uptake we synthesized MIP adjacent to the protein transduction domain, PTD4 (PMIP). Results: We have found that PMIP acts in a dominant-negative fashion, blocking both MUC1/β-catenin and MUC1/EGFR interactions. In addition, PMIP induces ligand-dependent reduction of EGFR levels. These effects correspond to a significant reduction in proliferation, migration, and invasion of metastatic breast cancer cells in vitro, and inhibition of tumor growth and recurrence in an established MDA-MB-231 immunocompromised (SCID) mouse model. Importantly, PMIP also inhibits genetically driven breast cancer progression, as injection of tumor-bearing MMTV-pyV mT transgenic mice with PMIP results in tumor regression and a significant inhibition of tumor growth rate. Conclusions: These data show that intracellular MUC1 peptides possess significant antitumor activity and have important clinical applications in the treatment of cancer.
Diminished serum Gc (vitamin D-binding protein) levels and increased Gc:G-actin complexes in a hamster model of fulminant hepatic necrosis
Authors: William M. Lee, David L. Emerson, William O. Young, Pascal J. Goldschmidt-Clermont, David J. Jollow, Robert M. Galbraith
Journal: Hepatology (1987)

Evidence for increased plasma levels of complexes containing Gc (vitamin D-binding protein) and cellular actin has been previously reported during fulminant hepatic necrosis in man. In order to study this process in more detail, we produced liver injury in hamsters using increasing doses of acetaminophen, with serial collection of sera for up to 168 hr after acetaminophen injection. Hamster Gc was purified using a three-step procedure and was shown to resemble closely human Gc. Polyclonal antihamster Gc was prepared and used in rocket immunoelectrophoresis and radial immunodiffusion studies for quantitation of total serum Gc and the percentage of Gc complexed with actin. Serum Gc levels were depressed in animals having liver damage, and the extent of depression 42 hr after acetaminophen correlated with the extent of elevation of AST. The proportion of the total Gc that was present in the complexed form increased in relation to the severity of the liver disease. In serial studies, diminution in Gc level preceded the rise in AST and increase in the percent complexed. These changes closely resemble observations in man and suggest that the hamster-acetaminophen hepatotoxicity model may be of value in further study of interactions of Gc with intracellular actin components and its role in actin homeostasis in conditions of massive tissue necrosis.
Prospective assessment of donor blood screening for antibody to hepatitis B core antigen as a means of preventing posttransfusion non-A, non-B, hepatitis
Authors: Melchor Hoyos, José V. Sarrión, Teresa Pérez-Castellanos, Martín Prieto, María L. Marty, Vicente Garrigues, Joaquín Berenguer
Journal: Hepatology (1989)

The relationship between donor status for antibody to hepatitis B core antigen and the occurrence of non-A, non-B posttransfusion hepatitis in the recipient was prospectively studied in 112 patients undergoing open-heart surgery who were followed for 6.5 months after surgery. Non-A, non-B posttransfusion hepatitis occurred in five (7.93%) of 63 patients who had received at least one anti-HBc-positive blood unit compared to seven (14.28%) of 49 patients who received anti-HBc-negative blood only. Statistical analysis revealed that the incidence of non-A, non-B posttransfusion hepatitis was independent of the use of blood positive for anti-HBc. Based upon these results and the high prevalence (17.3%) of anti-HBc among our blood donor population, the exclusion of anti-HBc-positive blood does not seem appropriate to achieve a reduction in the incidence of non-A, non-B posttransfusion hepatitis.
Improved diagnostic accuracy with 16-row multi-slice computed tomography coronary angiography
Authors: Nico R. Mollet, Filippo Cademartiri, Gabriel P. Krestin, Eugène P. McFadden, Chourmouzios A. Arampatzis, Patrick W. Serruys, Pim J. de Feyter
Journal: Journal of the American College of Cardiology (2004)