tbuckley/cabot-search huggingface dataset:
Insulin Resistance Syndrome in the Elderly
Authors: William A. Banks, Lisa M. Willoughby, David R. Thomas, John E. Morley
Journal: Diabetes Care (2007)

Hyperinsulinemic euglycemia, or insulin resistance syndrome (IRS), is associated with increased morbidity and mortality. Although thought to be associated with proinflammatory states, little work has been done in this area. Here, we determined the impact of IRS on functional, biochemical, metabolic, and inflammatory status in a high-risk population: elderly women in nursing homes.Functional, biochemical, metabolic, and inflammatory parameters were measured in 100 consecutive ambulatory, elderly women who resided in nursing homes. Diabetic subjects and residents with fasting blood glucose >or=110 mg/dl were excluded. Remaining residents were classified as insulin resistant (IR) (insulin >100 pmol/l) or non-IR (NIR).A total of 16 residents were IR and 53 NIR. No differences in functional status, BMI, renal function, C-reactive protein, or immune cell levels were found. Fasting blood glucose was higher in IR subjects ([means +/- SD] 94.1 +/- 8.1 vs. 87.9 +/- 8.2, P < 0.05), indicating a very mild glucose intolerance. Serum C-peptide (P < 0.05), amylin (P < 0.01), and leptin (P < 0.01), but not adiponectin or resistin, were higher in IR subjects. Higher leptin-to-BMI and insulin-to-C-peptide ratios suggested an increased percent body fat mass and altered clearance of insulin, respectively. Eleven of 13 cytokines had arithmetic elevations, but only tumor necrosis factor-alpha (TNF) reached statistical significance (P < 0.01). TNF and insulin levels were highly correlated.IRS in the healthiest of long-term care residents is relatively rare but is associated with mild glucose intolerance, increased percent body fat, altered insulin clearance, and a proinflammatory status as evidenced by an elevated TNF.
Abnormal Serum Immunoglobulins Occurring With Reticular Neoplasms in an Inbred Strain of Mouse
Authors: K R McIntire, L W Law
Journal: JNCI Journal of the National Cancer Institute (1967)

The reticular neoplasms occurring spontaneously in SJL/J mice exhibit a broad spectrum which includes both pleomorphic and monomorphic tumors. The former can be divided into classes of histiocyte-predominant, plasmacyte-predominant, or mixtures of the two, the latter can be separated into pure reticulum cell sarcoma (type A) and lymphocytic neoplasia. Of the 50 tumors reported here, 33 were tested for abnormal serum proteins and 19 had discrete elevations in the immunoglobulin, or paraproteinemia. Of these 19 with paraprotein, 11 were γF, 4 were γH, 1 was γG, and 3 had 2 different paraproteins. Of the 16 attempted transplants, 12 grew successfully and 6 of these have apparently produced the same type of protein in transplant. The production of paraprotein and the progressive tumor growth resulting in death of the mouse are evidence for malignancy in a lesion which looks more hyperplastic than neoplastic. These tumors should provide a new model system for the study of the carcinogenic process and its relation to cellular differentiation as determined by the production of paraprotein.
Sites of Formation of the Serum Proteins Transferrin and Hemopexin
Authors: G. J. Thorbecke, H. H. Liem, S. Knight, K. Cox, U. Muller-Eberhard
Journal: Journal of Clinical Investigation (1973)

Sites of synthesis of hemopexin and transferrin were determined by culturing various tissues of rabbits and monkeys in the presence of labeled amino acids. Labeling of the serum proteins was examined by means of autoradiographs of immunoelectrophoretic patterns as well as by precipitation in the test tubes employing immunospecific antisera. Good correlation was seen between the results obtained by the two different methods. The liver was found to be the only site of many tissues studied that synthesized hemopexin. Transferrin production was observed in the liver, submaxillary gland, lactating mammary gland, testis, and ovary.
FOREIGN BODIES IN THE OESOPHAGUS
Authors: F. H. Diggle
Journal: BMJ (1932)

it unexplained.. Hypertrophic spondylitis deformans the formation of osteophytes around the bodies of ertebrae, yet another form of osteo-arthritis, will not alt with here.different types which, for the present, may be led in the osteo-arthritic group are as foll6ws: igle major joint (possibly infective); (2) several major (rare);(3) major and several minor joints (hands); tinor joints (hands) alone involved; (5) spondylitis nans ; (6) osteochondritis dissecans. 3most tragic of cases treated at the clinic are the , patients crippled by spondylitis deformans, or ;o-called general infective arthritic cases.To my this type of arthritis requires separate study and retation.It is interesting, however, to note that of these unfortunate patients have, at the age of ie bones of a man of 50; their costal cartilages show sive calcification, while other senile degenerative res are present, suggesting that the disease has some olic basis.Another interesting observation I have is that many of these spondylitis deformans cases er cent.)show evidence of a chronic infective condi- or even abscess formation in the sacro-iliac joints.GOUT feature in " uratosis," or " osteo-arthritis urica e Germans, is the deposit of sodium urate crystals articular ends of the minor joints of the hand and occasionally in the joint of the big toe.iliographically, these deposits are indicated by well- d punched-out areas in the bone.Although these isually to be found in the superficial surface of tlar bone-that is, immediately under the cartilage- zed defects are occasionally situated in the actual substance.These small cavities may contain tls during the active stage of the disease, later to placed by granulation tissue, while in some cases are just empty spaces in the bone.There is reason lieve that the cavities noted in the head and neck femur, in many of the so-called osteo-arthritic hips, be of gouty origin.I have seen one case where gouty cavities in the bone have been replaced by .1 bone, either as the result of the attack quieting , or as a response to treatment.Further investigaon these lines might form a valuable indication as e effect of treatment.
Utilization of Pathway Signatures to Reveal Distinct Types of B Lymphoma in the Eμ-<i>myc</i> Model and Human Diffuse Large B-Cell Lymphoma
Authors: Seiichi Mori, Rachel E. Rempel, Jeffrey T. Chang, Guang Yao, Anand S. Lagoo, Anil Potti, Andrea Bild, Joseph R. Nevins
Journal: Cancer Research (2008)

The Emu-myc transgenic mouse has provided a valuable model for the study of B-cell lymphoma. Making use of gene expression analysis and, in particular, expression signatures of cell signaling pathway activation, we now show that several forms of B lymphoma can be identified in the Emu-myc mice associated with time of tumor onset. Furthermore, one form of Emu-myc tumor with pre-B character is shown to resemble human Burkitt lymphoma, whereas others exhibit more differentiated B-cell characteristics and show similarity with human diffuse large B-cell lymphoma in the pattern of gene expression, as well as oncogenic pathway activation. Importantly, we show that signatures of oncogenic pathway activity provide further dissection of the spectrum of diffuse large B-cell lymphoma, identifying a subset of patients who have very poor prognosis and could benefit from more aggressive or novel therapeutic strategies. Taken together, these studies provide insight into the complexity of the oncogenic process and a novel strategy for dissecting the heterogeneity of B lymphoma.
Radiographic scoring methods as outcome measures in rheumatoid arthritis: properties and advantages
Authors: S Boini, F Guillemin
Journal: Annals of the Rheumatic Diseases (2001)

Use of scored radiographs as an outcome measure can help estimate the progression of rheumatoid arthritis (RA). Radiographs not only provide permanent records with which to evaluate RA serially, but can also be randomised and blinded, a major advantage in clinical trials.Medline was searched for information about the principal methods of assessing joints affected by RA. Each technique was evaluated for its measurement properties, advantages, and limitations.The most commonly used methods are those devised by Sharp, Larsen, and van der Heijde/Sharp, and their variants. Methods based on the Sharp technique provide separate scores for erosion and for joint space narrowing. Larsen and variants, together with the Simple Erosion Narrowing Score (SENS) method, provide an overall score. Each method's measurement properties (feasibility, time consumption, etc) depend on the degree of detail it considers. Authors consistently recommend taking a posteroanterior view of hand and foot radiographs, and the use of trained raters. Intra- and interrater reliability values are generally higher than 0.70 (less often assessed by the intraclass correlation coefficient than the correlation coefficient). Sensitivity to change is calculated by several techniques (standardised response mean (SRM), adjusted SRM, minimal detectable change, smallest detectable difference). Most methods assessed with SRM reach a value of 0.80 or more.Standardised procedures are available for performing and reading radiographs in RA. The choice of scoring method depends on the time and staff available, and the required degree of reliability and sensitivity to change.
Involvement of intrasinusoidal hemostasis in the development of concanavalin a-induced hepatic injury in mice
Authors: Yuko Miyazawa, Hiroko Tsutsui, Hidekazu Mizuhara, Hiromi Fujiwara, Kenji Kaneda
Journal: Hepatology (1998)

Concanavalin A (Con A) stimulation induces T-cell activation-associated hepatic injury. This study is designed to show the involvement of microcirculatory disturbance in the pathogenesis. Con A administration led to prominent intrasinusoidal hemostasis, which consisted of erythrocyte agglutination, lymphocyte/neutrophil sticking to endothelial cells, and platelet aggregation and degranulation, resulting in a marked decrease in the intrahepatic blood flow and elevation of portal perfusion pressure. After hemostasis, confluent hepatic necrosis occurred within the congested area of liver parenchyma. Reduction in the extent of hemostasis by the treatment with heparin (thrombin inhibitor) or cyproheptadine (serotonin inhibitor) decreased hepatic injury. Pretreatment with either anti-tumor necrosis factor alfa (TNF-α) or anti-interferon gamma (IFN-γ) monoclonal antibody (MAb) moderately decreased hemostasis and hepatic injury, whereas combined use of two MAbs almost perfectly protected mice from these disorders. Complete obliteration of hemostasis and hepatic injury was also accomplished by the pretreatment with FK506 which suppressed TNF-α and IFN-γ production. Intrasinusoidal accumulation of leukocytes and platelets was, however, not blocked by FK506, indicating that Con A activities other than the stimulation of cytokine production are responsible for this event. The administration of anti-CD3 MAb, a T-cell stimulant without agglutination activities, which elevated plasma cytokine levels in a comparable degree without inducing prominent leukocyte infiltration, did not induce hepatic congestion and injury. These findings indicate that the agglutination activities of Con A and T-cell activation mediated TNF-α/IFN-γ production are both required for the induction of intrasinusoidal hemostasis, which is indispensable for the development of hepatic injury.
Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women
Authors: Elizabeth Sienkiewicz, Faidon Magkos, Konstantinos N. Aronis, Mary Brinkoetter, John P. Chamberland, Sharon Chou, Kalliopi M. Arampatzi, Chuanyun Gao, Anastasia Koniaris, Christos S. Mantzoros
Journal: Metabolism (2011)
Chemical Strategies for Stem Cell Biology and Regenerative Medicine
Authors: Saiyong Zhu, Wanguo Wei, Sheng Ding
Journal: Annual Review of Biomedical Engineering (2011)

Stem cell technology holds great promises for the cures of devastating diseases, injuries, aging, and even cancers as it is applied in regenerative medicine. Recent breakthroughs in the development of induced pluripotent stem cell techniques and efficient differentiation strategies have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells. Small molecules, which target specific signaling pathways and/or proteins, have been demonstrated to be particularly valuable for manipulating cell fate, state, and function. Such small molecules not only are useful in generating desired cell types in vitro for various applications but also could be further developed as conventional therapeutics to stimulate patients' endogenous cells to repair and regenerate in vivo. Here, we focus on recent progress in the use of small molecules in stem cell biology and regenerative medicine.
Matrix Metalloproteinase-9 Regulates Tumor Cell Invasion through Cleavage of Protease Nexin-1
Authors: Danmei Xu, Chad M. McKee, Yunhong Cao, Yunchuan Ding, Benedikt M. Kessler, Ruth J. Muschel
Journal: Cancer Research (2010)

Matrix metalloproteinase-9 (MMP-9) expression is known to enhance the invasion and metastasis of tumor cells. In previous work based on a proteomic screen, we identified the serpin protease nexin-1 (PN-1) as a potential target of MMP-9. Here, we show that PN-1 is a substrate for MMP-9 and establish a link between PN-1 degradation by MMP-9 and regulation of invasion. PN-1 levels increased in prostate carcinoma cells after downregulation of MMP-9 and in tissues of MMP-9-deficient mice, consistent with PN-1 degradation by MMP-9. We identified three MMP-9 cleavage sites in PN-1 and showed that mutations in those sites made PN-1 more resistant to MMP-9. Urokinase plasminogen activator (uPA) is inhibited by PN-1. MMP-9 augmented uPA activity in the medium of PC3-ML cells by degrading PN-1. Prostate cancer cells, overexpressing PN-1 or treated with MMP-9 shRNA, had reduced cell invasion in Matrigel. PN-1 siRNA restored uPA activity and the invasive capacity. PN-1 mutated in the serpin inhibitory domain, the reactive center loop, failed to inhibit uPA and to reduce Matrigel invasion. This study shows a novel molecular pathway in which MMP-9 regulates uPA activity and tumor cell invasion through cleavage of PN-1.
Testosterone's role in dominance, sex, and aggression: Why so controversial?
Authors: Douglas T. Kenrick, Alicia Barr
Journal: Behavioral and Brain Sciences (1998)

Testosterone's connection to sex differences and key evolutionary processes arouses controversy. Effects on humans and other species, though, are not robotically deterministic but are parts of complex interactions. We discuss the societal implications of these findings and consider how the naturalistic fallacy and the person–situation dichotomy contribute to misunderstandings here.
BMA calls on next government to avoid "dangerous" cuts to NHS
Authors: A. O'Dowd
Journal: BMJ (2009)

The UK’s next government must avoid hastily made cuts in health services or risk seriously damaging the NHS, doctors’ leaders have said.

The BMA, launching an early bid for the support of politicians before next year’s general election, has warned of the dangers of cutting NHS spending in what it calls a “slash and burn” way to trim public spending during the current economic recession.

In its general election manifesto, Standing up for Doctors—Standing up for Health , launched on 2 December, the BMA says that all political parties should acknowledge the value of the NHS, which it says provides better value for money than any similar healthcare system in …
Rhinosinusitis: Establishing definitions for clinical research and patient care
Authors: Eli O. Meltzer, Daniel L. Hamilos, James A. Hadley, Donald C. Lanza, Bradley F. Marple, Richard A. Nicklas, Claus Bachert, James Baraniuk, Fuad M. Baroody, Michael S. Benninger, Itzhak Brook, Badrul A. Chowdhury, Howard M. Druce, Stephen Durham, Berrylin Ferguson, Jack M. Gwaltney, Michael Kaliner, David W. Kennedy, Valerie Lund, Robert Naclerio, Ruby Pawankar, Jay F. Piccirillo, Patricia Rohane, Ronald Simon, Raymond G. Slavin, Alkis Togias, Ellen R. Wald, S. James Zinreich
Journal: Journal of Allergy and Clinical Immunology (2004)
Evidence by reactivity with hybridoma antibodies for a probable myeloid origin of peripheral blood cells active in natural cytotoxicity and antibody-dependent cell-mediated cytotoxicity.
Authors: H D Kay, D A Horwitz
Journal: Journal of Clinical Investigation (1980)

Lymphocytes with Fc receptors (FcR) for IgG active in natural cytotoxicity and antibody-dependent cellular cytotoxicity were separated into sheep erythrocyte rosetting (E+) and nonrosetting (E-) fractions, and examined for reactivity with the OK panel of hybridoma-produced monoclonal antibodies. Few cells in either the E+ FcR+ or the E- FcR+ fraction reacted with seven antibodies used to define T cells in various stages of differentiation (OK3, OKT4, OKT5, OKT6, OKT8, OKT9, OKT10). Neither fraction expressed an Ia-like antigen (detected by OKI1), but both were highly reactive with OKM1, an antibody that reacts with monocytes and granulocytes. Incubation of these cytotoxic effector cells with OKM1 plus complement abolished all cytotoxic reactivity, but incubation with a pan-T cell antibody (OKT3) plus complement had no significant effect. These cells were not monocyte precursors, because they could not be induced in vitro to develop macrophage characteristics. The data indicate that most cytotoxic effector cells in natural cytotoxicity and antibody-dependent cellular cytotoxicity are not in the T cell lineage, but have a myeloid origin.
Lack of Fibronectin-EDA Promotes Survival and Prevents Adverse Remodeling and Heart Function Deterioration After Myocardial Infarction
Authors: Fatih Arslan, Mirjam B. Smeets, Paul W. Riem Vis, Jacco C. Karper, Paul H. Quax, Lennart G. Bongartz, John H. Peters, Imo E. Hoefer, Pieter A. Doevendans, Gerard Pasterkamp, Dominique P. de Kleijn
Journal: Circulation Research (2011)

Rationale: The extracellular matrix may induce detrimental inflammatory responses on degradation, causing adverse cardiac remodeling and heart failure. The extracellular matrix protein fibronectin-EDA (EIIIA; EDA) is upregulated after tissue injury and may act as a “danger signal” for leukocytes to cause adverse cardiac remodeling after infarction. Objective: In the present study, we evaluated the role of EDA in regulation of postinfarct inflammation and repair after myocardial infarction. Methods and Results: Wild-type and EDA −/− mice underwent permanent ligation of the left anterior coronary artery. Despite equal infarct size between groups (38.2±4.6% versus 38.2±2.9% of left ventricle; P =0.985), EDA −/− mice exhibited less left ventricular dilatation and enhanced systolic performance compared with wild-type mice as assessed by serial cardiac MRI measurements. In addition, EDA −/− mice exhibited reduced fibrosis of the remote area without affecting collagen production, cross-linking, and deposition in the infarct area. Subsequently, ventricular contractility and relaxation was preserved in EDA −/− . At tissue level, EDA −/− mice showed reduced inflammation, metalloproteinase 2 and 9 activity, and myofibroblast transdifferentiation. Bone marrow transplantation experiments revealed that myocardium-induced EDA and not EDA from circulating cells regulates postinfarct remodeling. Finally, the absence of EDA reduced monocyte recruitment as well as monocytic Toll-like receptor 2 and CD49d expression after infarction. Conclusions: Our study demonstrated that parenchymal fn-EDA plays a critical role in adverse cardiac remodeling after infarction. Absence of fn-EDA enhances survival and cardiac performance by modulating matrix turnover and inflammation via leukocytes and fibroblasts after infarction.
Inhibitory Effects of Lectins and Lymphocyte Mitogens on Murine Lymphomas and Myelomas2
Authors: Peter Ralph, Ilona Nakoinz
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Inhibitory Effects of Lectins and Lymphocyte Mitogens on Murine Lymphomas and Myelomas Get access Peter Ralph, Peter Ralph Search for other works by this author on: Oxford Academic PubMed Google Scholar Ilona Nakoinz Ilona Nakoinz Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 883–890, https://doi.org/10.1093/jnci/51.3.883 Published: 01 September 1973 Article history Received: 02 March 1973 Accepted: 14 May 1973 Published: 01 September 1973
Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study.
Authors: R Trueworthy, J Shuster, T Look, W Crist, M Borowitz, A Carroll, L Frankel, M Harris, H Wagner, M Haggard
Journal: Journal of Clinical Oncology (1992)

PURPOSE Using the technique of recursive partitioning and amalgamation analysis with verification, the Pediatric Oncology Group (POG) investigated the independent prognostic significance of previously published prognostic factors significantly associated with event-free survival (EFS) in B-progenitor cell acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Age, leukocyte count, sex, immunophenotype (expression of cytoplasmic immunoglobulin [Ig] and of surface antigens CD10 and CD34), and DNA index (ratio of the flow cytometry-determined DNA content of leukemia cells to that of normal diploid cells) were the variables used in the evaluation of four antimetabolite-based chemotherapy regimens in 1,535 children with the newly diagnosed B-progenitor cell ALL between February 1986 and May 1990. RESULTS There were three subgroups at widely different risks of treatment failure. A DNA index greater than 1.16 was the most prognostic feature. The final prognostic subgrouping was as follows: (1) DNA index greater than 1.16; (2) DNA index less than or equal to 1.16, age less than 11.0 years, and leukocyte count less than 50 x 10(9)/L; and (3) DNA index less than or equal to 1.16, (age greater than 11.0 years, and/or leukocyte count greater than 50 x 10(9)/L). These groups made up 20%, 53%, and 27% of the patients and had 4-year EFS rates (SE) of 90.1% (6.3%), 80.5% (5.1%), and 50.4% (7.6%), respectively. CONCLUSIONS Use of the DNA index, leukocyte count, and age--data that are relatively inexpensive and simple to obtain--may be sufficient to stratify patients with B-progenitor cell ALL for risk-directed therapy. Patients at an extremely low risk of failing therapy (approximately 20% of cases in this study) can thus be identified and spared the toxic short-term and late effects of more intensive therapies that may be needed for children with less favorable clinical and biologic features.