tbuckley/cabot-search huggingface dataset:
A nephritogenic rat monoclonal antibody to mouse aminopeptidase A. Induction of massive albuminuria after a single intravenous injection.
Authors: K J Assmann, J P van Son, H B Dijkman, R A Koene
Journal: The Journal of Experimental Medicine (1992)

Antibodies directed against antigens present on renal epithelial cells can cause membranous glomerulonephritis in experimental animals, which closely resembles the human form of this disease. However, most antibodies produced so far fail to cause the persistent and severe proteinuria that is seen in humans. In our search for new antibodies of this kind, we have now produced a monoclonal antibody (mAb) against mouse aminopeptidase A, a hydrolase that is present in the mouse kidney. The mAb (ASD-4) was prepared by fusion of mouse myeloma cells with splenocytes of Lou rats immunized with brush border (BB) membranes from mouse kidneys. ASD-4 is of the IgG1 subclass and reacts with a 140-kD protein as demonstrated by immunoprecipitation on radiolabeled BB membranes. In indirect immunofluorescence and immunoelectronmicroscopy of normal mouse kidneys, ASD-4 was diffusely present on the BB of the S1 and S2 segments of the proximal tubules, and on the cell membranes of the glomerular visceral epithelia. It also bound to cell membranes of nonglomerular endothelia, smooth muscle cells of arteries, and juxtaglomerular cells. After injection of ASD-4 into normal mice, an immediate homogeneous binding to the capillary wall was seen that gradually changed into a fine granular pattern after 1 d. This glomerular binding was followed by binding to the BB and basolateral membranes of the convoluted proximal tubules. Immediately after injection of ASD-4, a dose-dependent albuminuria occurred that lasted for at least 16 d. ASD-4 is thus a new rat mAb against a well-defined renal epithelial antigen that causes not only membranous glomerulonephritis after a single injection in the mouse, but also severe albuminuria.
Angiogenesis Inhibitor, TNP-470, Prevents Diet-Induced and Genetic Obesity in Mice
Authors: Ebba Bråkenhielm, Renhai Cao, Bihu Gao, Bo Angelin, Barbara Cannon, Paolo Parini, Yihai Cao
Journal: Circulation Research (2004)

Adipose tissue growth has been proposed to involve recruitment of new blood vessels. Here, we test the hypothesis that delivery of an angiogenesis inhibitor in mice may prevent diet-induced obesity, the most common type of obesity in humans. We show that systemic administration of a selective angiogenesis inhibitor, TNP-470 (AGM-1470), prevents obesity in high caloric diet-fed wt mice as well as in genetically leptin-deficient ob/ob mice. Inhibition of obesity in mice by TNP-470 involves a reduction of vascularity in the adipose tissue. This therapeutic strategy appears to selectively affect the growth of adipose tissue as measured by the ratio between total fat and lean body mass. Interestingly, the treatment with TNP-470 results in decreased serum levels of low-density lipoprotein cholesterol. Furthermore, insulin levels are reduced, which indicates increased insulin sensitivity, suggesting that angiogenesis inhibitors may prevent the development of type II diabetes. Our findings suggest that similarly to growth and organogenesis in other tissues, adipose tissue growth is dependent on angiogenesis. Our observations may have conceptual implications for the prevention of obesity and related disorders.
BI-14 * GENOMIC PROFILING OF A PREDICTIVE SIGNATURE FOR MET-TARGETED THERAPY IN GLIOBLASTOMA
Authors: J. Johnson, M. L. Ascierto, D. Newsome, S. Mittal, L. Kang, M. Briggs, K. Tanner, M. E. Berens, F. M. Marincola, G. F. Vande Woude, Q. Xie
Journal: Neuro-Oncology (2014)

The success of molecular targeted therapy against cancer depends on discovering the tumor driver genes and the molecular determinants that control the pathway activity. Glioblastoma (GBM) is one of the most devastating cancers due to its highly infiltrating nature, and MET pathway activation is a major cause of invasion in both primary and recurrent tumors. Because MET inhibitors are in clinical trials against GBM, there may be clinical utility from developing more effective patient enrollment strategies tailored to targeted therapeutics. Previously, we reported (Xie et al., PNAS 2012) that GBM tumors with high levels of hepatocyte growth factor (HGF) often display HGF-autocrine activation through its receptor MET, which is a key molecular feature in sensitivity to MET inhibitors. In this study, we sought to develop a molecular signature that can be used as a biomarker to identify GBM patients whose tumor would be vulnerable to treatment with MET inhibitors. Because GBM is a heterogeneous disease in which drug response in the individual patient can be influenced by a variety of different mechanisms, the expression of a single gene was not anticipated to be sufficient to pinpoint sensitivity to the drug; rather, a hypothesis-driven, biomarker-based molecular signature would likely be of a higher value. We analyzed genomic data from GBM patients in The Cancer Genome Atlas (TCGA) Network as well as from preclinical tumor models. We found that GBM tumors sensitive to MET inhibitors share common genomic profiles. More importantly, using patient-derived xenograft models, a 25-gene molecular signature was identified that predicted sensitivity to MET inhibitors. Our findings are a proof-of-concept for the use of genomic signatures to identify GBM patients with greater vulnerability for MET-targeted therapy.
Hierarchical Organization of Prostate Cancer Cells in Xenograft Tumors: The CD44+α2β1+ Cell Population Is Enriched in Tumor-Initiating Cells
Authors: Lubna Patrawala, Tammy Calhoun-Davis, Robin Schneider-Broussard, Dean G. Tang
Journal: Cancer Research (2007)

Abstract Prostate cancer cells are heterogeneous in their tumorigenicity. For example, the side population cells isolated from LAPC9 xenografts are 100 to 1,000 times more tumorigenic than the corresponding non–side population cells. Highly purified CD44+ prostate cancer cells from several xenografts are also enriched in prostate cancer stem/progenitor cells. Because the CD44+ prostate cancer cell population is still heterogeneous, we wonder whether we could further enrich for tumorigenic prostate cancer cells in this population using other markers. Integrin α2β1 has been proposed to mark a population of normal human prostate stem cells. Therefore, we first asked whether the α2β1+/hi cells in prostate tumors might also represent prostate cancer stem cells. Highly purified (≥98%) α2β1+/hi cells from three human xenograft tumors, Du145, LAPC4, and LAPC9, show higher clonal and clonogenic potential than the α2β1−/lo cells in vitro. However, when injected into the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse prostate or s.c., the α2β1+/hi prostate cancer cells are no more tumorigenic than the α2β1−/lo cells. Immunofluorescence studies reveal that CD44 and α2β1 identify an overlapping and inclusive population of prostate cancer cells in that ∼70% of α2β1+/hi cells are CD44+ and 20% to 30% of CD44+ cells are distributed in the α2β1−/lo cell population. Subsequently, we sorted out CD44+α2β1+/hi, CD44+α2β1−/lo, CD44−α2β1+/hi, and CD44−α2β1−/lo cells from LAPC9 tumors and carried out tumorigenicity experiments. The results revealed a hierarchy in tumorigenic potential in the order of CD44+α2β1+/hi ≈ CD44+α2β1−/lo &amp;gt; CD44−α2β1+/hi ≫ CD44−α2β1−/lo. These observations together suggest that prostate cancer cells are organized as a hierarchy. [Cancer Res 2007;67(14):6796–805]
Gallium-67 as a diagnostic tool in the evaluation of peripheral pulmonary lesions
Authors: B. T. le Roux, A. E. Houlder
Journal: Thorax (1974)

<b>le Roux, B. T., and Houlder, A. E. (1974).</b><i>Thorax</i>, <b>29</b>, 355-358. <b>Gallium-67 as a diagnostic tool in the evaluation of peripheral pulmonary lesions.</b> While Gallium-67 shows a high affinity for primary pulmonary tumours, benign pulmonary lesions also concentrate the isotope. In 50 consecutive patients in whom the diagnosis of pulmonary carcinoma was not achieved by other means, the exhibition of <sup>67</sup>Ga showed a positive scan in 36, of whom three, on histological evidence, certainly did not have a pulmonary carcinoma, and in three others radiographic diminution in the extent of the peripheral pulmonary lesion makes most unlikely the diagnosis of carcinoma. In seven of 14 patients in whom the scan was negative it was judged necessary to undertake surgical management. Scanning with <sup>67</sup>Ga may modify the extent of surgical resection in some with a negative scan but does not establish the diagnosis of carcinoma in those with a positive scan, is unsafe as a screening test on which to base the decision on the need for referral to a thoracic surgeon, and in particular does not distinguish between the three common causes of `chronic lung abscess9—chronic destructive pneumonia, cavitated carcinoma, and tuberculosis with cavitation and without tubercle bacilli in the sputum.
Colonoscopy perforation rate, mechanisms and outcome: from diagnostic to therapeutic colonoscopy
Authors: V. Panteris, J. Haringsma, E. Kuipers
Journal: Endoscopy (2009)

See also: Commentaire de travail de V. Panteris et al., pp. 941Endoscopy 2009; 41(11): 1008-1008DOI: 10.1055/s-0032-1306753
Lectin-driven maturation of cytotoxic effector cells: the nature of effector memory.
Authors: A K Chakravarty, W R Clark
Journal: The Journal of Experimental Medicine (1977)

In an attempt to define further the activation of effector T-cell function with concanavalin A (Con A), we examined the ability of Con A to generate effector memory in mouse lymph node cells in vitro. In the course of these studies, it became necessary to define parameters by which memory could be defined. These parameters include length of time of exposure to signal required to generate full cytotoxic function; time of onset and kinetics of blast cell formation; requirement for DNA synthesis; sensitivity to the drug 5'-bromodeoxyuridine; and kinetics of the cytotoxic response to alloantigen. By these criteria, mouse lymph node cells exposed 12 days previously to Con A behave qualitatively differently from unprimed mouse lymphocytes. We found that the time of onset and kinetics of DNA synthesis could not be used to distinguish primary and secondary cytotoxic responses. We propose that the parameters defined in these stidues can be applied generally in determining whether a given cytotoxic response involves primed (memory) or unprimed cells.
A Retinoic Acid–Induced Clonal Cell Line Derived From Multipotential P19 Embryonal Carcinoma Cells Expresses Smooth Muscle Characteristics
Authors: Randal S. Blank, Ellen A. Swartz, Maria M. Thompson, Eric N. Olson, Gary K. Owens
Journal: Circulation Research (1995)

Abstract Despite intense interest in understanding the differentiation of vascular smooth muscle, very little is known about the cellular and molecular mechanisms that control differentiation of this cell type. Progress in this field has been hampered by the lack of an inducible in vitro system for study of the early steps of smooth muscle differentiation. In this study, we describe a model system in which multipotential mouse P19 embryonal carcinoma cells (P19s) can be induced to express multiple characteristics of differentiated smooth muscle. Treatment of P19s with retinoic acid was associated with profound changes in cell morphology and with the appearance at high frequency of smooth muscle α-actin–positive cells that were absent or present at extremely low frequency in parental P19s. A clonal line derived from retinoic acid–treated P19s (9E11G) stably expressed multiple characteristics of differentiated smooth muscle, including smooth muscle–specific isoforms of α-actin and myosin heavy chain, as well as functional responses to the contractile agonists phenylephrine, angiotensin II, ATP, bradykinin, histamine, platelet-derived growth factor (PDGF)-AA, and PDGF-BB. Additionally, 9E11G cells expressed transcripts for MHox , a muscle homeobox gene expressed in smooth, cardiac, and skeletal muscles, but not the skeletal muscle–specific regulatory factors, MyoD and myogenin. Results demonstrate that retinoic acid treatment of multipotential P19 cells is associated with formation of cell lines that stably express multiple properties of differentiated smooth muscle. It remains to be determined whether retinoic acid has induced commitment to a smooth muscle cell lineage as opposed to directly (or indirectly) activating genes characteristic of differentiated smooth muscle cells. However, results suggest that this cell system may be of use in attempting to identify genes involved in controlling smooth muscle differentiation and/or lineage determination.
Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study
Authors: Isabelle Quéré, Thomas V Perneger, Jacqueline Zittoun, Hélène Bellet, Jean-Christophe Gris, Jean-Pierre Daurès, Jean-François Schved, Eric Mercier, Jean-Pierre Laroche, Michel Dauzat, Henri Bounameaux, Charles Janbon, Philippe de Moerloose
Journal: The Lancet (2002)
Peptide-MHC heterodimers show that thymic positive selection requires a more restricted set of self-peptides than negative selection
Authors: Jeremy Juang, Peter J.R. Ebert, Dan Feng, K. Christopher Garcia, Michelle Krogsgaard, Mark M. Davis
Journal: The Journal of Experimental Medicine (2010)

T cell selection and maturation in the thymus depends on the interactions between T cell receptors (TCRs) and different self-peptide-major histocompatibility complex (pMHC) molecules. We show that the affinity of the OT-I TCR for its endogenous positively selecting ligands, Catnb-H-2Kb and Cappa1-H-2Kb, is significantly lower than for previously reported positively selecting altered peptide ligands. To understand how these extremely weak endogenous ligands produce signals in maturing thymocytes, we generated soluble monomeric and dimeric peptide-H-2Kb ligands. Soluble monomeric ovalbumin (OVA)-Kb molecules elicited no detectable signaling in OT-I thymocytes, whereas heterodimers of OVA-Kb paired with positively selecting or nonselecting endogenous peptides, but not an engineered null peptide, induced deletion. In contrast, dimer-induced positive selection was much more sensitive to the identity of the partner peptide. Catnb-Kb-Catnb-Kb homodimers, but not heterodimers of Catnb-Kb paired with a nonselecting peptide-Kb, induced positive selection, even though both ligands bind the OT-I TCR with detectable affinity. Thus, both positive and negative selection can be driven by dimeric but not monomeric ligands. In addition, positive selection has much more stringent requirements for the partner self-pMHC.
Reduction of Circulating Soluble Fms-Like Tyrosine Kinase-1 Plays a Significant Role in Renal Dysfunction–Associated Aggravation of Atherosclerosis
Authors: Kenji Onoue, Shiro Uemura, Yukiji Takeda, Satoshi Somekawa, Hajime Iwama, Keiichi Imagawa, Taku Nishida, Yoshinobu Morikawa, Yasuhiro Takemoto, Osamu Asai, Tsunenari Soeda, Satoshi Okayama, Kenichi Ishigami, Kimihiko Nakatani, Hiroyuki Kawata, Manabu Horii, Tamio Nakajima, Yasuhiro Akai, Masayuki Iwano, Yoshihiko Saito
Journal: Circulation (2009)

Renal dysfunction is commonly accompanied by a worsening of atherosclerosis; however, the underlying molecular mechanism is not fully understood. We examined the role played by soluble fms-like tyrosine kinase-1 (sFlt-1), an endogenous antagonist of the proatherogenic cytokine placental growth factor (PlGF), in the worsening of atherosclerosis in patients with renal dysfunction and in an animal model of renal failure.In this study, 329 patients who received cardiac catheterization and 76 patients who underwent renal biopsy were enrolled. Both plasma sFlt-1 levels and renal sFlt-1 mRNA expression were positively correlated with estimated glomerular filtration rate (P<0.01). The PlGF/sFlt-1 ratio was negatively correlated with estimated glomerular filtration rate (P<0.01), whereas plasma PlGF levels were not affected by it. The PlGF/sFlt-1 ratio was significantly higher in patients with multivessel coronary artery disease than in patients with single-vessel or no coronary artery disease. The reduction of circulating sFlt-1 and renal sFlt-1 mRNA levels was confirmed in five-sixths (5/6)-nephrectomized apolipoprotein E-deficient mice that developed experimental renal dysfunction. Atherosclerotic plaque area and macrophage infiltration into the plaque were significantly higher in 5/6-nephrectomized apolipoprotein E-deficient mice than in control mice, but replacement therapy with recombinant sFlt-1 significantly reduced both plaque formation and macrophage infiltration.The present study demonstrates that a reduction in the circulating levels of sFlt-1 is associated with the worsening of atherosclerosis that accompanies renal dysfunction.
Comparison of the Prognostic Value of Assessing Tumor Diameter Versus Tumor Volume at Diagnosis or in Response to Initial Chemotherapy in Rhabdomyosarcoma
Authors: Andrea Ferrari, Rosalba Miceli, Cristina Meazza, Michela Casanova, Francesca Favini, Carlo Morosi, Giovanna Trecate, Alfonso Marchianò, Roberto Luksch, Graziella Cefalo, Monica Terenziani, Filippo Spreafico, Daniela Polastri, Marta Podda, Serena Catania, Elisabetta Schiavello, Patrizia Giannatempo, Lorenza Gandola, Maura Massimino, Luigi Mariani
Journal: Journal of Clinical Oncology (2010)

In this study on a series of 205 patients with rhabdomyosarcoma, we investigated whether the prognostic effect of tumor size, at diagnosis or in terms of tumor response after induction chemotherapy, differed when tumor diameter or tumor volume were considered.Tumor size was assessed radiologically at diagnosis and, for the 108 patients with measurable disease, after three courses of chemotherapy. The analysis was based on multivariable models (linear for association between size and patient/tumor characteristics, Cox for association with survival). The predictive performance of the Cox model (estimated by V measure) was compared for the tumor's diameter and volume.Initial tumor size was significantly larger in male or older patients and in T2 or alveolar tumors, but was not associated with the achievement of complete surgical resection. Initial tumor size significantly influenced overall survival. The risk of death was comparable for tumors 10 cm in maximum diameter and 194.0 cm(3) in volume. The predictive performance of the Cox model was much the same when the tumor's diameter or volume was considered. Tumor response was a significant predictor of survival, again irrespective of the type of tumor measurement considered.In our analysis, initial tumor size and tumor response were significant prognostic factors in rhabdomyosarcoma, regardless of whether tumor diameter or volume was considered. Three-dimensional tumor assessment was of no greater prognostic value than one-dimensional assessment, neither initially nor after induction treatment.
Development, structure and function of the cranial suspensory ligaments of the mammalian gonads in a cross-species perspective; their possible role in effecting disturbed testicular descent
Authors: P van der Schoot
Journal: Human Reproduction Update (1996)

The present review aims to present a perspective on a relatively unknown part of the mammalian internal genitalia: their cranial suspensory apparatus. This apparatus shows wide divergence of development when examined during the fetal period or during adulthood, in males or females, or in individuals across a variety of species. In rats and other mammalian species the apparatus undergoes a distinct pattern of sexually dimorphic development and fetal testicular androgens are proposed to play a key role in this process. Extensive development of this suspensory apparatus in females is argued to be a part of the anatomical adaptations of the genital apparatus to support the internal genitalia throughout pregnancy, including the relatively enormous growth towards the time of parturition. Minor development of this apparatus in males is judged to be a part of the anatomical requirements allowing developing testes to become displaced from the dorsal abdominal wall during the first stage of testicular descent. Extensive development of this suspensory apparatus in males generally seems to hinder testicular descent. Accordingly, the apparatus is well developed in so-called testicond species which do not show testis descent as a part of their normal male genital development. Furthermore, arguments are adduced that inappropriate and extensive development in species with testis descent may be a key aetiological factor in the disturbance of this process. Diagnosis and treatment of human cryptorchidism might profit from including an analysis of the development and function of (remnants of) the cranial testicular and epididymal suspensory apparatus. Keywords: cranial suspensory apparatus/cryptorchidism/genital development/testicular descent
Transformation of Tonsil Lymphocytes by Epstein-Barr Virus2
Authors: Naoki Yamamoto, Takato Katsuki, Yorio Hinuma
Journal: JNCI Journal of the National Cancer Institute (1976)

Tonsil lymphocytes obtained from children and adults at tonsillectomy were examined for susceptibility to infection with Epstein-Barr virus (EBV) in vitro. Of 37 specimens, 24 (65%) were transformed by EBV. Rate of transformation was higher in the cells from younger children than in those from older children and adults, but the susceptibility was not directly correlated to the titer of antibody against EBV in donor serum. All 22 transformed tonsil cell lines tested were carrying EBV-associated nuclear antigen, and B of them produced cytoplasmic IgA in 15–45% of cells. The results suggest that tonsil lymphocytes are targets of EBV.
Association of hypomagnesemia with inferior survival in a phase III, randomized study of cetuximab plus best supportive care versus best supportive care alone: NCIC CTG/AGITG CO.17
Authors: M.M. Vickers, C.S. Karapetis, D. Tu, C.J. O'Callaghan, T.J. Price, N.C. Tebbutt, G. Van Hazel, J.D. Shapiro, N. Pavlakis, P. Gibbs, J. Blondal, U. Lee, J.M. Meharchand, R.L. Burkes, S.H. Rubin, J. Simes, J.R. Zalcberg, M.J. Moore, L. Zhu, D.J. Jonker
Journal: Annals of Oncology (2012)
Inhibition of the growth of Rickettsia prowazekii in cultured fibroblasts by lymphokines.
Authors: J Turco, H H Winkler
Journal: The Journal of Experimental Medicine (1983)

The effect of lymphokine treatment of mouse and human fibroblast cell lines on the growth of Rickettsia prowazekii within the fibroblasts was studied. Treatment of mouse L929 cells with concanavalin A- or antigen-induced mouse lymphokines both before and after infection with R. prowazekii led to clearance of the rickettsiae from a substantial proportion of the cells and suppression of rickettsial growth in those cells which remained infected. Similar but less dramatic anti-rickettsial effects were observed in L929 cells treated with mouse lymphokines either only before or after infection with rickettsiae. Mouse lymphokine treatment of L929 cells had similar anti-rickettsial effects on the avirulent E strain and the virulent Breinl strain of R. prowazekii. Addition of cycloheximide or emetine to L929 cells at the same time as the lymphokines markedly suppressed the inhibition of rickettsial growth by the lymphokines. Mouse lymphokine treatment inhibited rickettsial survival and growth in mouse 3T3-A31 cells as well as in mouse L929 cells, but had no effect on rickettsial survival and growth in human foreskin fibroblasts. Conversely, concanavalin A-induced human lymphokines inhibited rickettsial survival and growth in human foreskin fibroblasts but had no effect on rickettsial survival and growth in mouse L929 cells. The rickettsia inhibitory activity in concanavalin A-induced mouse lymphokines was destroyed by heating the lymphokines at 80 degrees C for 10 min or by holding the lymphokines at pH 2 for 24 h but was retained after heating at 56 degrees C for 30 min.