tbuckley/cabot-search huggingface dataset:
Interleukin 6 Dependence of Anti-DNA Antibody Production: Evidence for Two Pathways of Autoantibody Formation in Pristane-induced Lupus
Authors: Hanno B. Richards, Minoru Satoh, Melody Shaw, Claude Libert, Valeria Poli, Westley H. Reeves
Journal: The Journal of Experimental Medicine (1998)

Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6–deficient (−/−) and –intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, –double-stranded (ds)DNA, and -chromatin antibodies in IL-6+/+, but not IL-6−/− mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not −/−, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred &amp;gt;5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6−/− and IL-6+/+ mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses.
Human sperm devoid of PLC, zeta 1 fail to induce Ca2+ release and are unable to initiate the first step of embryo development
Authors: Sook-Young Yoon, Teru Jellerette, Ana Maria Salicioni, Hoi Chang Lee, Myung-sik Yoo, Kevin Coward, John Parrington, Daniel Grow, Jose B. Cibelli, Pablo E. Visconti, Jesse Mager, Rafael A. Fissore
Journal: Journal of Clinical Investigation (2008)

Egg activation, which is the first step in the initiation of embryo development, involves both completion of meiosis and progression into mitotic cycles. In mammals, the fertilizing sperm delivers the activating signal, which consists of oscillations in free cytosolic Ca2+ concentration ([Ca2+]i). Intracytoplasmic sperm injection (ICSI) is a technique that in vitro fertilization clinics use to treat a myriad of male factor infertility cases. Importantly, some patients who repeatedly fail ICSI also fail to induce egg activation and are, therefore, sterile. Here, we have found that sperm from patients who repeatedly failed ICSI were unable to induce [Ca2+]i oscillations in mouse eggs. We have also shown that PLC, zeta 1 (PLCZ1), the sperm protein thought to induce [Ca2+]i oscillations, was localized to the equatorial region of wild-type sperm heads but was undetectable in sperm from patients who had failed ICSI. The absence of PLCZ1 in these patients was further confirmed by Western blot, although genomic sequencing failed to reveal conclusive PLCZ1 mutations. Using mouse eggs, we reproduced the failure of sperm from these patients to induce egg activation and rescued it by injection of mouse Plcz1 mRNA. Together, our results indicate that the inability of human sperm to initiate [Ca2+]i oscillations leads to failure of egg activation and sterility and that abnormal PLCZ1 expression underlies this functional defect.
The applied anatomy of the lateral ligament complex of the ankle joint
Authors: H. Evans Robson
Journal: British Journal of Sports Medicine (1971)

<h3>Background</h3> The prevalence of pial arterial supply to cranial dural arteriovenous fistulas (dAVF) and its implication in the management of these fistulas is not well characterized. We performed a retrospective study to characterize pial arterial supply to dural arteriovenous fistulas and the implications for treatment. <h3>Methods</h3> Consecutive patients evaluated over a 12-year period were retrospectively reviewed. Angiograms were reviewed to characterize dAVF angioarchitecture and the presence of pial artery supply. Pial artery supply was categorized as dilated pre-existing dural branches and pure pial supply. We then studied the association between pial artery supply and clinical, angiographic, and treatment features. <h3>Results</h3> A total of 201 patients were included of which 27 (13.4%) had pial artery supply. Of these, 11 had supply from dilated pre-existing dural branches, nine had pure pial supply,and seven had both. There was a higher rate of dAVF rupture in the pial supply group (30.8% vs 9.8%, P=0.003) and these fistulas had a higher rate of Borden 2 and 3 (88.9% vs 38.4%, P&lt;0.0001). Fistulas with pial artery supply had similar rates of endovascular and gamma knife treatment, but were more likely to undergo surgery than those without pial supply (25.9% vs 10.4%, P=0.03). Major complication rates were similar between groups (0% vs 1.1%, P=0.55). <h3>Conclusions</h3> More than 10% of dAVFs also have pial supply but this is not a contraindication to embolization. In our study pure pial supply was associated with a more aggressive fistula and was most common in tentorial dAVFs.
Radiation Therapy with Tositumomab (B1) Anti-CD20 Monoclonal Antibody Initiates Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase–Dependent Cell Death that Overcomes Resistance to Apoptosis
Authors: Andrey Ivanov, Sergei Krysov, Mark S. Cragg, Tim Illidge
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The use of targeted radiation therapy (RT) in conjunction with anti-CD20 monoclonal antibodies (mAb) delivers high clinical response rates in B-cell lymphomas as part of radioimmunotherapy. The mechanisms underlying these impressive responses, particularly in patients whose lymphomas have become refractory to chemotherapy, are poorly understood. Experimental Design: In this study, we have investigated the signaling pathways and mode of cell death induced in B-cell lymphoma cells after the combination of RT and either type I (rituximab) or type II (tositumomab/B1) anti-CD20 mAb. Results: Increased tumor cell death was observed when RT was combined with tositumomab, but not rituximab. This additive cell death was found to be mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)–dependent and could be reversed with mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitors, as well as small interfering RNA targeting MEK1/2. Furthermore, we found that this increased death was associated with ERK1/2 nuclear accumulation after tositumomab treatment, which was enhanced in combination with RT. Importantly, although Bcl-2 overexpression resulted in resistance to RT-induced apoptosis, it had no effect on the tumor cell death induced by tositumomab plus RT, indicating a nonapoptotic form of cell death. Conclusions: These findings indicate that RT and type II anti-CD20 mAb combine to stimulate a prodeath function of the MEK-ERK1/2 pathway, which is able to overcome apoptotic resistance potentially explaining the efficacy of this modality in treating patients with chemoresistant disease.
Altered T Cell Receptor Ligands Trigger a Subset of Early T Cell Signals
Authors: Joshua D Rabinowitz, Craig Beeson, Christoph Wülfing, Keri Tate, Paul M Allen, Mark M Davis, Harden M McConnell
Journal: Immunity (1996)

TCR ligands are complexes of peptides and MHC proteins on the surfaces of APCs. Some of these ligands cause T cell proliferation (agonists), while others block it (antagonists). We compared the acid release, calcium flux, and proliferation response of helper T cells to a variety of ligands. We found that all agonist ligands but not most antagonist ligands trigger acid release, a general indicator of early cellular activation. Only a subset of ligands triggering acid release cause sustained calcium flux, and only a subset of these ligands cause T cell proliferation. Antagonist ligands and anti-CD4 antibodies both effectively block T cell proliferation. However, significantly greater antagonist ligand or antibody concentrations are required to block acid release and initial calcium influx. These data demonstrate a hierarchy of early T cell signaling steps and show that altered TCR ligands can initiate some steps while blocking the completion of others.
Follicular Helper CD4 T Cells (T<sub>FH</sub>)
Authors: Shane Crotty
Journal: Annual Review of Immunology (2011)

T cell help to B cells is a fundamental aspect of adaptive immunity and the generation of immunological memory. Follicular helper CD4 T (T(FH)) cells are the specialized providers of B cell help. T(FH) cells depend on expression of the master regulator transcription factor Bcl6. Distinguishing features of T(FH) cells are the expression of CXCR5, PD-1, SAP (SH2D1A), IL-21, and ICOS, among other molecules, and the absence of Blimp-1 (prdm1). T(FH) cells are important for the formation of germinal centers. Once germinal centers are formed, T(FH) cells are needed to maintain them and to regulate germinal center B cell differentiation into plasma cells and memory B cells. This review covers T(FH) differentiation, T(FH) functions, and human T(FH) cells, discussing recent progress and areas of uncertainty or disagreement in the literature, and it debates the developmental relationship between T(FH) cells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).
Molecular epidemiology of Acinetobacter baumannii and Acinetobacter nosocomialis in Germany over a 5-year period (2005–2009)
Authors: X. Schleicher, P.G. Higgins, H. Wisplinghoff, B. Körber-Irrgang, M. Kresken, H. Seifert
Journal: Clinical Microbiology and Infection (2012)
The pseudomembranous colitis associated with clindamycin therapy--a viral colitis.
Authors: H W Steer
Journal: Gut (1975)

Four patients are described who developed pseudomembranous colitis in association with clindamycin therapy. Rectal biopsies from two patients were studied with the electron microscope and compared with the ultrastructural appearance of the rectal mucosa from seven normal people. Ultrastructural evidence for a viral colitis was obtained. The significance of the clindamycin therapy to the viral colitis and the contribution of the viral colitis to the clinical state are discussed.
Cigarette Smoking and Ozone-Associated Emergency Department Use for Asthma by Adults in New York City
Authors: CARA CASSINO, KAZUHIKO ITO, IRA BADER, CARLO CIOTOLI, GEORGE THURSTON, JOAN REIBMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The association between ambient ozone (O3) and hospital use for asthma in children and adults is well documented. The question remains of whether there are susceptible subpopulations of asthmatic individuals who are particularly vulnerable to high O3 levels. Because tobacco use was prevalent in our cohort of inner-city adult asthmatic individuals (n = 1,216) in New York City (NYC), we investigated whether cigarette smoking was an effect modifier for asthma morbidity. We examined the relationship between personal tobacco use and O3-associated emergency department (ED) use for asthma in public hospitals in NYC. Three subpopulations were defined: never smokers (0 pack-yr), heavy smokers ( ⩾ 13 pack-yr) and light smokers ( < 13 pack-yr). Time-series regression analysis of ED use for asthma and daily O3 levels was done while controlling for temperature, seasonal/long-term trends, and day-of-week effects. Heavy smokers displayed an increased relative risk (RR) of ED visits for asthma in response to increases in 2-d lagged O3 levels (RR per 50 ppb O3 = 1.72; 95% confidence interval: 1.13 to 2.62). Logistic regression analysis confirmed that heavy cigarette use was a predictor of ED use for asthma following days with high O3 levels. Although adverse health effects of ambient O3 have also been documented in asthma populations not using cigarettes (e.g., children), our results suggest that in adult asthmatic individuals, heavy personal tobacco use may be an effect modifier for O3-associated morbidity.
Myofibrillar Architecture in Engineered Cardiac Myocytes
Authors: Kevin Kit Parker, John Tan, Christopher S. Chen, Leslie Tung
Journal: Circulation Research (2008)

Morphogenesis is often considered a function of transcriptional synchrony and the spatial limits of diffusing mitogens; however, physical constrainment by the cell microenvironment represents an additional mechanism for regulating self-assembly of subcellular structures. We asked whether myocyte shape is a distinct signal that potentiates the organization of myofibrillar arrays in cardiac muscle myocytes. We engineered the shape of neonatal rat ventricular myocytes by culturing them on microfabricated fibronectin islands, where they spread and assumed the shape of the island. Myofibrillogenesis followed, both spatially and temporally, the assembly of unique actin networks whose architecture was predictable given the shape of the island. Subsequently, the z lines of the sarcomeres aligned and registered in distinct patterns in different regions of the myocytes in such a way that orthogonal axes of contraction could be distinctly engineered. These data suggest that physical constrainment of muscle cells by extracellular matrix may be an important regulator of myofibrillar organization.
A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association
Authors: WG Austen, JE Edwards, RL Frye, GG Gensini, VL Gott, LS Griffith, DC McGoon, ML Murphy, BB Roe
Journal: Circulation (1975)
Nitrous Oxide—Oxygen Sedation for Minor Surgery
Authors: Glen C. Griffin
Journal: JAMA (1981)

Nitrous oxide-oxygen sedation has been used safely in a pediatric office for approximately 3,000 uncomfortable procedures such as laceration repairs in children and teenagers. Fear and apprehension were decreased, resulting in happier children, parents, and medical personnel. We describe a system and technique for safely utilizing nitrous oxide-oxygen sedation.  ( JAMA 1981;245:2411-2413)
New Strategies in Non–Small Cell Lung Cancer: Improving Outcomes in Chemoradiotherapy for Locally Advanced Disease
Authors: Ramesh Rengan, Amit M. Maity, James P. Stevenson, Stephen M. Hahn
Journal: Clinical Cancer Research (2011)

Abstract The past decade has seen significant breakthroughs in our knowledge of the tumor biology of non–small cell lung cancer (NSCLC). Signaling pathways that are vital for tumor growth have been identified and have been effectively targeted for pharmacologic intervention. Furthermore, advances in imaging and treatment delivery have allowed radiation oncologists to deliver therapy more precisely to mobile tumors, while minimizing the dose to surrounding critical structures. This article summarizes the implications of these advances for the patient with unresectable locally advanced NSCLC and highlights ongoing work to improve clinical outcomes in this disease. Clin Cancer Res; 17(13); 4192–9. ©2011 AACR.
Topical prostaglandin E2 in the treatment of chronic leg ulcers—a pilot study
Authors: G. ERIKSSON, M. TORNGREN, A. ALY, C. JOHANSSON
Journal: British Journal of Dermatology (1988)

The results of treatment with topical PGE2 dispersed in hydrocolloid granules, in nine patients with chronic leg ulcers is reported. The healing process was evaluated by stereophotogrammetry, which enables objective measurements of ulcer area and volume. Ulcers in eight patients healed completely and that in the ninth, almost completely. These results suggest that topical PGE2 has a beneficial effect in the treatment of leg ulcers.
Cell Division Cycle 25B Phosphatase Is Essential for Benzo(<i>a</i>)Pyrene-7,8-Diol-9,10-Epoxide–Induced Neoplastic Transformation
Authors: Sanjay K. Srivastava, Pallavi Bansal, Tetsuya Oguri, John S. Lazo, Shivendra V. Singh
Journal: Cancer Research (2007)

Abstract Cell division cycle 25B (Cdc25B) phosphatase controls entry into mitosis and regulates recovery from G2-M checkpoint-induced arrest. In the present study, we show that exposure of diploid mouse embryonic fibroblasts (MEF) to the ultimate carcinogen anti-benzo(a)pyrene (BP)-7,8-diol-9,10-epoxide (anti-BPDE) resulted in a concentration- and time-dependent increase in Cdc25B protein levels. Chronic exposure of wild-type (Cdc25B+/+) MEFs to anti-BPDE (0.1 μmol/L) caused neoplastic transformation characterized by colony formation in culture and tumor production in nude mice. In contrast, the Cdc25B null MEFs were resistant to anti-BPDE–induced transformation. Furthermore, a carcinogenic dose of the parent hydrocarbon (BP) increased Cdc25B protein levels in the target organ, lung. The biological importance of elevated Cdc25B levels was documented by the early reentry into mitosis of cells overexpressing ectopic Cdc25B levels even in the presence of DNA damage following anti-BPDE exposure, whereas control cells resumed only after DNA damage was repaired. We conclude that Cdc25B has an essential role in anti-BPDE–induced neoplastic transformation, including regulation of cell cycle resumption in the presence of DNA damage. [Cancer Res 2007;67(19):9150–7]
Inhibition of Micrometastatic Prostate Cancer Cell Spread in Animal Models By 213Bilabeled Multiple Targeted α Radioimmunoconjugates
Authors: Yong Li, Emma Song, Syed M. Abbas Rizvi, Carl A. Power, Julia Beretov, Chand Raja, Paul J. Cozzi, Alfred Morgenstern, Christos Apostolidis, Barry J. Allen, Pamela J. Russell
Journal: Clinical Cancer Research (2009)

To investigate the therapeutic potential of 213Bilabeled multiple targeted alpha-radioimmunoconjugates for treating prostate cancer (CaP) micrometastases in mouse models.PC-3 CaP cells were implanted s.c., in the prostate, and intratibially in NODSCID mice. The expression of multiple tumor-associated antigens on tumor xenografts and micrometastases was detected by immunohistochemistry. Targeting vectors were two monoclonal antibodies, and a plasminogen activator inhibitor type 2 that binds to cell surface urokinase plasminogen activator, labeled with 213Bi using standard methodology. In vivo efficacy of multiple alpha conjugates (MTAT) at different activities was evaluated in these mouse models. Tumor growth was monitored during observations and local regional lymph node metastases were assessed at the end of experiments.The take rate of PC-3 cells was 100% for each route of injection. The tumor-associated antigens (MUC1, urokinase plasminogen activator, and BLCA-38) were heterogeneously expressed on primary tumors and metastatic cancer clusters at transit. A single i.p. injection of MTAT (test) at high and low doses caused regression of the growth of primary tumors and prevented local lymph node metastases in a concentration-dependent fashion; it also caused cancer cells to undergo necrosis and apoptosis.Our results suggest that MTAT can impede primary PC-3 CaP growth at three different sites in vivo through induction of apoptosis, and can prevent the spread of cancer cells and target lymph node micrometastases in a concentration-dependent manner. MTAT, by targeting multiple antigens, can overcome heterogeneous antigen expression to kill small CaP cell clusters, thus providing a potent therapy for micrometastases.
Ultrasound for gastroenterologists.
Authors: R Vallance
Journal: Gut (1997)

<h3>Abstract</h3> Amyotrophic lateral sclerosis (ALS) is a multi-system disease characterized primarily by progressive muscle weakness. Cognitive dysfunction is commonly observed in patients, however factors influencing risk for cognitive dysfunction remain elusive. Using sparse canonical correlation analysis (sCCA), an unsupervised machine-learning technique, we observed that single nucleotide polymorphisms collectively associate with baseline cognitive performance in a large ALS patient cohort (N=327) from the multicenter Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium. We demonstrate that a polygenic risk score derived using sCCA relates to longitudinal cognitive decline in the same cohort, and also to <i>in vivo</i> cortical thinning in the orbital frontal cortex, anterior cingulate cortex, lateral temporal cortex, premotor cortex, and hippocampus (N=90) as well as <i>post mortem</i> motor cortical neuronal loss (N=87) in independent ALS cohorts from the University of Pennsylvania Integrated Neurodegenerative Disease Biobank. Our findings suggest that common genetic polymorphisms may exert a polygenic contribution to the risk of cortical disease vulnerability and cognitive dysfunction in ALS.
Cartilage specific collagen activates macrophages and the alternative pathway of complement: evidence for an immunopathogenic concept of rheumatoid arthritis.
Authors: H M Hanauske-Abel, B F Pontz, H U Schorlemmer
Journal: Annals of the Rheumatic Diseases (1982)

We studied the effect of human interstitial collagen types I, II, and III on serum-free cultured mouse macrophages and on the complement classical and alternative pathways in human and guinea-pig serum. Type II collagen produced a dose-dependent consumption and conversion of C3 and factor B both in the homologous and in the heterologous system. This effect on the alternative pathway was reproduced in genetically C4-deficient guinea-pig serum and could be triggered by native, triple helical type II molecules, by their component alpha chains, and the CNBr peptide mixture. Addition of type II collagen to the mouse macrophage cultures induced not only a dose- and time-dependent secretion of lysosomal enzymes, but also the generation of a supernatant factor cytotoxic for mouse mastocytoma P 815 cells. Collagen of types I and III were conspicuously less active or inactive in all assays. The studies demonstrate properties of the collagen specific for cartilage which, on a molecular level, suggest its direct, local participation in the production and perpetuation of rheumatoid arthritis.
Increasing Inspired Oxygen to Decrease Surgical Site Infection
Authors: E. Patchen Dellinger
Journal: JAMA (2005)

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