tbuckley/cabot-search huggingface dataset:
Juvenile General Paralysis
Authors: W. L. Milligan
Journal: BMJ (1948)

MEDICAL JOUYRNALinterval being four days.In our case blindness set in ,immediately after the accident, and atrophy was distinct after a fortnight.Concerning the prognosis of these cases there has been general agreement (Traquair) that if no signs of improve- ment in visual acuity occur during the first four weeks no further change can be expected.But in our patient there was a rapid and almost complete recovery as late as five months after the injury.This is difficult to explain; it is contrary to all experience that recovery should have started after so long a time.One might thinik of a hysteri- cal fixation of an original organic blindness, but nothing was observed in the general behaviour of the patient to support this, and there were no psychogenic elements.There were, on the other hand, optic atrophy and a tran- ,sitory scotoma-findings which do not permit a functional explanation.It is likely that the primary site of the lesion was in or near the anterior chiasmal angle, affecting mainly the ,right optic nerve but also damaging the crossed fibres of the left.It is interesting to note that the temporal-field defect of the left eye gradually diminished and had entirely Wdisappeared after the relapse.We will therefore have to assume that on this occasion the chiasma had been spared, the lesion being restricted to the right optic nerve. SummaryA case is reported in which blindness and optic atrophy in the right eye, with a temporal-field defect in the left eye, &ollowed a fall in an epileptic fit.X-ray examinations of the gull were negative.There was no fracture.Not less than five months after the injury normal visual acuity with full visual fields in the left eye were re-established;Iduring this period of recovery central vision was the last to return to normal.The temporal-field defect in the left eye was at the same time greatly reduced.Shortly afterwards, following a trivial blow on the face, his sight and visual-field condition deteriorated, a gradually extend- ing central scotoma appeared, and visual acuity fell rapidly -,ntil the right eye became blind again.There was no temporalield defect in the left eye at this time.Atrophy of the right disk remained unchanged during the whole period.There was no further change one year later.
Cetuximab Attenuates Its Cytotoxic and Radiosensitizing Potential by Inducing Fibronectin Biosynthesis
Authors: Iris Eke, Katja Storch, Mechthild Krause, Nils Cordes
Journal: Cancer Research (2013)

Abstract Inherent and acquired resistance to targeted therapeutics continues to emerge as a major clinical obstacle. For example, resistance to EGF receptor targeting occurs commonly, more so than was expected, on the basis of preclinical work. Given emerging evidence that cancer cell–substrate interactions are important determinants of therapeutic sensitivity, we examined the impact of cell–fibronectin interactions on the efficacy of the EGF receptor antibody cetuximab, which is used widely for lung cancer treatment. Our results revealed the potential for cell–fibronectin interactions to induce radioresistance of human non–small cell lung cancer cells. Cell adhesion to fibronectin enhanced tumor cell radioresistance and attenuated the cytotoxic and radiosensitizing effects of cetuximab. Both in vitro and in vivo, we found that cetuximab treatment led to a remarkable induction of fibronectin biosynthesis. Mechanistic analyses revealed the induction was mediated by a p38–MAPK–ATF2 signaling pathway and that RNAi-mediated inhibition of fibronectin could elevate the cytotoxic and radiosensitizing potential of cetuximab. Taken together, our findings show how cell adhesion blunts cetuximab, which, by inducing fibronectin, generates a self-attenuating mechanism of drug resistance. Cancer Res; 73(19); 5869–79. ©2013 AACR.
Myocardial Expression of a Dominant-Negative Form of Daxx Decreases Infarct Size and Attenuates Apoptosis in an In Vivo Mouse Model of Ischemia/Reperfusion Injury
Authors: François Roubille, Stéphane Combes, Juani Leal-Sanchez, Christian Barrère;, Frédéric Cransac, Catherine Sportouch-Dukhan, Gérald Gahide, Isabelle Serre, Elodie Kupfer, Sylvain Richard, Anne-Odile Hueber, Joël Nargeot, Christophe Piot, Stéphanie Barrère-Lemaire
Journal: Circulation (2007)

Background— Apoptosis has been described extensively in acute myocardial infarction and chronic heart failure. Because Daxx (death-associated protein) appears to be essential for stress-induced cell death and acts as an antisurvival molecule, we tested the hypothesis that Daxx is involved in myocardial ischemia/reperfusion–induced cell death in vivo. Methods and Results— Transgenic mice overexpressing a dominant-negative form of Daxx (Daxx-DN) under the control of the β-actin promoter and control wild-type mice underwent an ischemia/reperfusion protocol: 40 minutes of left coronary artery occlusion and 60 minutes of reperfusion. Area at risk and infarct size were measured after dual staining by triphenyltetrazolium chloride and phthalocyanine blue dye. Apoptosis was measured in the ischemic versus the nonischemic part of the left ventricle by terminal deoxynucleotidyl transferase–mediated dUTP biotin nick end labeling staining, enzyme-linked immunosorbent assay, and Western blotting of caspase-3, caspase-8, and poly(ADP-ribose) polymerase. The mitogen-activated protein kinase status was investigated by Western blot analysis. Comparison between groups was assessed by ANOVA or Student t test (statistical significance: P &lt;0.05). Left ventricle tissues from transgenic mice expressed Daxx-DN at the protein level. Area at risk/left ventricle values were comparable among groups. Infarct size/area at risk was 45% reduced in Daxx-DN versus wild-type mice ( P &lt;0.001). This cardioprotection was maintained for a 4-hour reperfusion. Ischemia/reperfusion-induced apoptosis was significantly decreased and ERK1/2 prosurvival pathway was activated in ischemic Daxx-DN hearts. Conclusions— Our study clearly indicates that Daxx participates in myocardial ischemia/reperfusion proapoptotic signaling in vivo.
AXL Is a Key Regulator of Inherent and Chemotherapy-Induced Invasion and Predicts a Poor Clinical Outcome in Early-Stage Colon Cancer
Authors: Philip D. Dunne, Darragh G. McArt, Jaine K. Blayney, Murugan Kalimutho, Samanda Greer, Tingting Wang, Supriya Srivastava, Chee Wee Ong, Ken Arthur, Maurice Loughrey, Keara Redmond, Daniel B. Longley, Manuel Salto-Tellez, Patrick G. Johnston, Sandra Van Schaeybroeck
Journal: Clinical Cancer Research (2013)

Despite the use of 5-fluorouracil (5-FU)-based adjuvant treatments, a large proportion of patients with high-risk stage II/III colorectal cancer will relapse. Thus, novel therapeutic strategies are needed for early-stage colorectal cancer. Residual micrometastatic disease from the primary tumor is a major cause of patient relapse.
Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice.
Authors: H Ishida, T Muchamuel, S Sakaguchi, S Andrade, S Menon, M Howard
Journal: The Journal of Experimental Medicine (1994)

We have previously shown that continuous administration of anti-interleukin 10 (anti-IL-10) antibodies (Abs) to BALB/c mice modifies endogenous levels of autoantibodies, tumor necrosis factor alpha (TNF-alpha), and interferon gamma, three immune mediators known to affect the development of autoimmunity in "lupus-prone" New Zealand black/white (NZB/W)F1 mice. To explore the consequences of IL-10 neutralization in NZB/W F1 mice, animals were injected two to three times per week from birth until 8-10 mo of age with anti-IL-10 Abs or with isotype control Abs. Anti-IL-10 treatment substantially delayed onset of autoimmunity in NZB/W F1 mice as monitored either by overall survival, or by development of proteinuria, glomerulonephritis, or autoantibodies. Survival at 9 mo was increased from 10 to 80% in anti-IL-10-treated mice relative to Ig isotype-treated controls. This protection against autoimmunity appeared to be due to an anti-IL-10-induced upregulation of endogenous TNF-alpha, since anti-IL-10-protected NZB/W F1 mice rapidly developed autoimmunity when neutralizing anti-TNF-alpha Abs were introduced at 30 wk along with the anti-IL-10 treatment. Consistent with the protective role of anti-IL-10 treatment in these experiments, continuous administration of IL-10 from 4 until 38 wk of age accelerated the onset of autoimmunity in NZB/W F1 mice. The same period of continuous IL-10 administration did not appear to be toxic to, or cause development of lupus-like autoimmunity in normal BALB/c mice. These data suggest that IL-10 antagonists may be beneficial in the treatment of human systemic lupus erythematosus.
The Hypertension Paradox — More Uncontrolled Disease despite Improved Therapy
Authors: Aram V. Chobanian
Journal: New England Journal of Medicine (2009)

In the 2009 Shattuck Lecture, Aram Chobanian describes the tremendous progress that has been made in the recognition and treatment of hypertension in the past 60 years. He lays out the basis of an apparent paradox: despite better recognition and treatment, the prevalence of untreated hypertension continues to increase.
FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study
Authors: Anu Suomalainen, Jenni M Elo, Kirsi H Pietiläinen, Anna H Hakonen, Ksenia Sevastianova, Mari Korpela, Pirjo Isohanni, Sanna K Marjavaara, Tiina Tyni, Sari Kiuru-Enari, Helena Pihko, Niklas Darin, Katrin Õunap, Leo AJ Kluijtmans, Anders Paetau, Jana Buzkova, Laurence A Bindoff, Johanna Annunen-Rasila, Johanna Uusimaa, Aila Rissanen, Hannele Yki-Järvinen, Michio Hirano, Mar Tulinius, Jan Smeitink, Henna Tyynismaa
Journal: The Lancet Neurology (2011)
Lovastatin Inhibits Transforming Growth Factor-β1 Expression in Diabetic Rat Glomeruli and Cultured Rat Mesangial Cells
Authors: SUNG IL KIM, DONG CHEOL HAN, HI BAHL LEE
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Diabetic nephropathy is a leading cause of end-stage renal disease and is characterized by excessive deposition of extracellular matrix (ECM) proteins in the glomeruli. Transforming growth factor-β (TGF-β) is the major mediator of excessive accumulation of ECM proteins in diabetic nephropathy through upregulation of genes encoding ECM proteins as well as downregulation of genes for ECM-degrading enzymes. It has been shown that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, delays the onset and progression of different models of experimental nephropathy. To evaluate the effect of lovastatin on the development and progression of diabetic nephropathy, streptozotocin-induced diabetic rats were studied for 12 mo. In untreated diabetic rats, there were significant increases in blood glucose, urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression in the glomeruli compared with normal control rats treated with citrate buffer only. Treatment with lovastatin in diabetic rats significantly suppressed the increase in urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression despite high blood glucose levels. To elucidate the mechanisms of the renal effects of lovastatin, rat mesangial cells were cultured under control (5.5 mM) or high (30 mM) glucose with lovastatin alone, mevalonate alone, or with both. Under high glucose, TGF-β1 and fibronectin mRNA and proteins were upregulated. These high glucose-induced changes were suppressed by lovastatin (10 μM) and nearly completely restored by mevalonate (100 μM). These results suggest that lovastatin has a direct cellular effect independent of a cholesterol-lowering effect and delays the onset and progression of diabetic nephropathy, at least in part, through suppression of glomerular expression of TGF-β1.
Risk Factors for Falls among Elderly Persons Living in the Community
Authors: Mary E. Tinetti, Mark Speechley, Sandra F. Ginter
Journal: New England Journal of Medicine (1988)

To study risk factors for falling, we conducted a one-year prospective investigation, using a sample of 336 persons at least 75 years of age who were living in the community. All subjects underwent detailed clinical evaluation, including standardized measures of mental status, strength, reflexes, balance, and gait; in addition, we inspected their homes for environmental hazards. Falls and their circumstances were identified during bimonthly telephone calls. During one year of follow-up, 108 subjects (32 percent) fell at least once; 24 percent of those who fell had serious injuries and 6 percent had fractures. Predisposing factors for falls were identified in linear-logistic models. The adjusted odds ratio for sedative use was 28.3; for cognitive impairment, 5.0; for disability of the lower extremities, 3.8; for palmomental reflex, 3.0; for abnormalities of balance and gait, 1.9; and for foot problems, 1.8; the lower bounds of the 95 percent confidence intervals were 1 or more for all variables. The risk of falling increased linearly with the number of risk factors, from 8 percent with none to 78 percent with four or more risk factors (P<0.0001). About 10 percent of the falls occurred during acute illness, 5 percent during hazardous activity, and 44 percent in the presence of environmental hazards. We conclude that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling. (N Engl J Med 1988; 319:1701–7.)
Glucocorticoid Receptor Beta (GCR)-beta Regulates HDAC2 Expression in Bronchoalveolar Lavage Cells (BAL) and Peripheral Blood Mononuclear Cells (PBMC) of Asthmatics
Authors: L. Li, D.Y. Leung, E. Goleva
Journal: Journal of Allergy and Clinical Immunology (2009)

RATIONALE: Hormone-bound glucocorticoid receptor (GCR)-alpha translocates to the cell nuclei, induces histone H4 acetylation and recruits histone deacetylase-2 (HDAC2) to the transcription complex to suppress inflammatory genes. Reduced HDAC2 expression and activity is correlated with steroid resistance. The role of GCR-beta (the dominant negative isoform of steroid receptor) in this process has not been addressed. METHODS: Expression of HDAC1, HDAC2, GCR-alpha and GCR-beta was measured by real time PCR in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMC) from steroid resistant (SR) versus steroid sensitive (SS) asthmatics, as well in DO11.10 cell line transduced with bicistronic GFP-GCR-beta or GFP construct. GCR-beta gene expression was selectively inhibited in BAL cells by small interfering RNA (siRNA). RESULTS: BAL cells from SR asthmatics had significantly higher levels of GCR-beta compared to SS asthmatics (n = 7, p = 0.041). Levels of HDAC2 mRNA were significantly decreased in BAL cells from SR as compared to SS asthmatics (n = 7, p = 0.0379); but no difference was observed in PBMC between these two groups. Overexpression of GCR-beta in DO11.10 T cells significantly reduced HDAC2 mRNA levels but had no effect on HDAC1. Silencing of GCR-beta mRNA in BAL cells from asthmatics resulted in significantly enhanced HDAC2 mRNA expression (8377.35 ± 533.35 vs. 5092.08 ± 680.24 HDAC2 ng/18sRNA, n = 3, p = 0.008 for cells transfected with GCR-beta siRNA vs. negative control siRNA, respectively). CONCLUSIONS: This study suggests that GCR-beta acts as a repressor that controls the expression of HDAC2 and highlights a novel mechanism by which GCR-beta further promotes steroid insensitivity.
Comparison of Gene Sets for Expression Profiling: Prediction of Metastasis from Low-Malignant Breast Cancer
Authors: Mads Thomassen, Qihua Tan, Freyja Eiriksdottir, Martin Bak, Søren Cold, Torben A. Kruse
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In the low-risk group of breast cancer patients, a subgroup experiences metastatic recurrence of the disease. The aim of this study was to examine the performance of gene sets, developed mainly from high-risk tumors, in a group of low-malignant tumors. Experimental Design: Twenty-six tumors from low-risk patients and 34 low-malignant T2 tumors from patients with slightly higher risk have been examined by genome-wide gene expression analysis. Nine prognostic gene sets were tested in this data set. Results: A 32-gene profile (HUMAC32) that accurately predicts metastasis has previously been developed from this data set. In the present study, six of the eight other gene sets have prognostic power in the low-malignant patient group, whereas two have no prognostic value. Despite a relatively small overlap between gene sets, there is high concordance of classification of samples. This, together with analysis of functional gene groups, indicates that the same pathways may be represented by several of the gene sets. However, the results suggest that low-risk patients may be classified more accurately with gene signatures developed especially for this patient group. Conclusion: Several gene sets, mainly developed in high-risk cancers, predict metastasis from low-malignant cancer.
Malignant Transformation of Mouse Connective Tissue Grown in Diffusion Chambers
Authors: Emma Shelton, V. J. Evans, G. A. Parker
Journal: JNCI Journal of the National Cancer Institute (1963)

Journal Article Malignant Transformation of Mouse Connective Tissue Grown in Diffusion Chambers Get access Emma Shelton, Emma Shelton Laboratory of Biochemistry and Laboratory of General Biology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar V. J. Evans, V. J. Evans Laboratory of Biochemistry and Laboratory of General Biology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar G. A. Parker G. A. Parker Laboratory of Biochemistry and Laboratory of General Biology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 30, Issue 2, February 1963, Pages 377–391, https://doi.org/10.1093/jnci/30.2.377 Published: 01 February 1963 Article history Received: 26 September 1962 Published: 01 February 1963
Meta-analysis of Neuroblastomas Reveals a Skewed <i>ALK</i> Mutation Spectrum in Tumors with <i>MYCN</i> Amplification
Authors: Sara De Brouwer, Katleen De Preter, Candy Kumps, Piotr Zabrocki, Michaël Porcu, Ellen M. Westerhout, Arjan Lakeman, Jo Vandesompele, Jasmien Hoebeeck, Tom Van Maerken, Anne De Paepe, Geneviève Laureys, Johannes H. Schulte, Alexander Schramm, Caroline Van Den Broecke, Joëlle Vermeulen, Nadine Van Roy, Klaus Beiske, Marleen Renard, Rosa Noguera, Olivier Delattre, Isabelle Janoueix-Lerosey, Per Kogner, Tommy Martinsson, Akira Nakagawara, Miki Ohira, Huib Caron, Angelika Eggert, Jan Cools, Rogier Versteeg, Frank Speleman
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Activating mutations of the anaplastic lymphoma kinase (ALK) were recently described in neuroblastoma. We carried out a meta-analysis of 709 neuroblastoma tumors to determine their frequency and mutation spectrum in relation to genomic and clinical parameters, and studied the prognostic significance of ALK copy number and expression. Experimental Design: The frequency and type of ALK mutations, copy number gain, and expression were analyzed in a new series of 254 neuroblastoma tumors. Data from 455 published cases were used for further in-depth analysis. Results: ALK mutations were present in 6.9% of 709 investigated tumors, and mutations were found in similar frequencies in favorable [International Neuroblastoma Staging System (INSS) 1, 2, and 4S; 5.7%] and unfavorable (INSS 3 and 4; 7.5%) neuroblastomas (P = 0.087). Two hotspot mutations, at positions R1275 and F1174, were observed (49% and 34.7% of the mutated cases, respectively). Interestingly, the F1174 mutations occurred in a high proportion of MYCN-amplified cases (P = 0.001), and this combined occurrence was associated with a particular poor outcome, suggesting a positive cooperative effect between both aberrations. Furthermore, the F1174L mutant was characterized by a higher degree of autophosphorylation and a more potent transforming capacity as compared with the R1275Q mutant. Chromosome 2p gains, including the ALK locus (91.8%), were associated with a significantly increased ALK expression, which was also correlated with poor survival. Conclusions: ALK mutations occur in equal frequencies across all genomic subtypes, but F1174L mutants are observed in a higher frequency of MYCN-amplified tumors and show increased transforming capacity as compared with the R1275Q mutants. Clin Cancer Res; 16(17); 4353–62. ©2010 AACR.
Remarkable resemblance in the mode of transmission of HCV infection among haemodialysis patients and IVDAs
Authors: A K Saxena
Journal: Gut (2003)

Hepatitis C virus (HCV) infection is widespread among patients on long term haemodialysis (HD) and among intravenous drug abusers (IVDAs). However, there appear to be striking similarities in the mode of transmission between the two groups as both are at high risk for parenterally transmitted HCV infection.

The indispensable requirement of having a vascular access site possibly adds to the risk of acquiring HCV infection among patients on long term HD through nosocomial transmission, especially in high HCV prevalence units. Preliminary data suggest that among various types of vascular access used for HD, arteriovenous fistula …
Molecular Pathways: Targeted α-Particle Radiation Therapy
Authors: Kwamena E. Baidoo, Kwon Yong, Martin W. Brechbiel
Journal: Clinical Cancer Research (2012)

Abstract An α-particle, a 4He nucleus, is exquisitely cytotoxic and indifferent to many limitations associated with conventional chemo- and radiotherapy. The exquisite cytotoxicity of α-radiation, the result of its high mean energy deposition [high linear energy transfer (LET)] and limited range in tissue, provides for a highly controlled therapeutic modality that can be targeted to selected malignant cells [targeted α-therapy (TAT)] with minimal normal tissue effects. A burgeoning interest in the development of TAT is buoyed by the increasing number of ongoing clinical trials worldwide. The short path length renders α-emitters suitable for treatment and management of minimal disease such as micrometastases or residual tumor after surgical debulking, hematologic cancers, infections, and compartmental cancers such as ovarian cancer or neoplastic meningitis. Yet, despite decades of study of high LET radiation, the mechanistic pathways of the effects of this modality remain not well defined. The modality is effectively presumed to follow a simple therapeutic mechanism centered on catastrophic double-strand DNA breaks without full examination of the actual molecular pathways and targets that are activated that directly affect cell survival or death. This Molecular Pathways article provides an overview of the mechanisms and pathways that are involved in the response to and repair of TAT-induced DNA damage as currently understood. Finally, this article highlights the current state of clinical translation of TAT as well as other high-LET radionuclide radiation therapy using α-emitters such as 225Ac, 211At, 213Bi, 212Pb, and 223Ra. Clin Cancer Res; 19(3); 530–7. ©2012 AACR.
THE COLONY MORPHOLOGY OF TUBERCLE BACILLI
Authors: Kenneth C. Smithburn
Journal: The Journal of Experimental Medicine (1935)

1. Smooth, round, shiny, non-granular, and non-spreading colonies have been observed in cultures of virulent tubercle bacilli freshly isolated from eight human sources other than sputum. The classification of six of these strains as of human type was established by inoculation into rabbits and guinea pigs. 2. The 3 per cent NaOH or 6 per cent H(2)SO(4) frequently used in the isolation of tubercle bacilli are definitely unfavorable to the development of smooth colonies. 3. It was observed that smooth colonies are produced in greater number when the pH of the medium (Corper's egg yolk-glycerine) is adjusted to a point near to but slightly on the acid side of neutral.