tbuckley/cabot-search huggingface dataset:
Head and neck cancer cells and xenografts are very sensitive to palytoxin: decrease of c-jun n-terminale kinase-3 expression enhances palytoxin toxicity
Authors: Tibor Görögh, László Bèress, Elgar S Quabius, Petra Ambrosch, Markus Hoffmann
Journal: Molecular Cancer (2013)

Palytoxin (PTX), a marine toxin isolated from the Cnidaria (zooanthid) Palythoa caribaeorum is one of the most potent non-protein substances known. It is a very complex molecule that presents both lipophilic and hydrophilic areas. The effect of PTX was investigated in a series of experiments conducted in head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts. Cell viability, and gene expression of the sodium/potassium-transporting ATPase subumit alpha1 (ATP1AL1) and GAPDH were analyzed in HNSCC cells and normal epithelial cells after treatment with PTX using cytotoxicity-, clonogenic-, and enzyme inhibitor assays as well as RT-PCR and Northern Blotting. For xenograft experiments severe combined immunodeficient (SCID) mice were used to analyze tumor regression. The data were statistically analyzed using One-Way Annova (SPSS vs20). Significant toxic effects were observed in tumor cells treated with PTX (LD50 of 1.5 to 3.5 ng/ml) in contrast to normal cells. In tumor cells PTX affected both the release of LDH and the expression of the sodium/potassium-transporting ATPase subunit alpha1 gene suggesting loss of cellular integrity, primarily of the plasma membrane. Furthermore, strong repression of the c-Jun N-terminal kinase 3 (JNK3) mRNA expression was found in carcinoma cells which correlated with enhanced toxicity of PTX suggesting an essential role of the mitogen activated protein kinase (MAPK)/JNK signalling cascades pathway in the mechanisms of HNSCC cell resistance to PTX. In mice inoculated with carcinoma cells, injections of PTX into the xenografted tumors resulted within 24 days in extensive tumor destruction in 75% of the treated animals (LD50 of 68 ng/kg to 83 ng/kg) while no tumor regression occurred in control animals. These results clearly provide evidence that PTX possesses preferential toxicity for head and neck carcinoma cells and therefore it is worth further studying its impact which may extend our knowledge of the biology of head and neck cancer.
Rapid evolution in a conserved gene family. Evolution of the actin gene family in the sea urchin genus Heliocidaris and related genera
Authors: J C Kissinger, J H Hahn, R A Raff
Journal: Molecular Biology and Evolution (1997)

Camarodont sea urchins possess a rapidly evolving actin gene family whose members are expressed in distinct cell lineages in a developmentally regulated fashion. Evolutionary changes in the actin gene family of echinoids include alterations in number of family members, site of expression, and gene linkage, and a dichotomy between rapidly and slowly evolving isoform-specific 3' untranslated regions. We present sequence comparisons and an analysis of the actin gene family in two congeneric sea urchins that develop in radically different modes, Heliocidaris erythrogramma and H. tuberculata. The sequences of several actin genes from the related species Lytechinus variegatus are also presented. We compare the features of the Heliocidaris and Lytechinus actin genes to those of the the actin gene families of other closely related sea urchins and discuss the nature of the evolutionary changes among sea urchin actins and their relationship to developmental mode.
Reliability of naevus counts in identifying individuals at high risk of malignant melanoma
Authors: J.E. BYLES, D. HENNRIKUS, R. SANSON-FISHER, P. HERSEY
Journal: British Journal of Dermatology (1994)

The majority of deaths from malignant melanoma could be prevented by regular screening of at‐risk individuals. However, the feasibility of introducing active screening programmes depends on the reliability of criteria for identifying those individuals who are at increased risk. Several case‐control studies indicate that one of the most important risk Factors is the number of benign pigmented naevi. This criterion might constitute a practical means of identifying individuals suitable for inclusion in an active screening programme. The aim of this study was to assess the reliability of using naevus counts as an indicator of risk. Two possible methods of assessment were compared: assessment by trained interviewers, and assessment by experienced dermatologists. The results suggest that this criterion may not be as practical or reliable as originally anticipated. Interviewer naevus counts correlated poorly with dermatologists' assessments (kappa =0·19). Counts by dermatologists of the number of naevi on the left arm differed by up to nine naevi, although most counts were within four naevi of each other. There was reasonable correlation between naevus counts on the left arm and those on the whole body (r= 0·71). However, the relationship was not perfect. Selection of individuals for screening solely based on the number of naevi on the left arm may exclude many people with high total body counts but relatively low left arm counts.
Prevalence and Risk Factors of Diabetic Nephropathy in an Urban South Indian Population
Authors: Ranjit Unnikrishnan, Mohan Rema, Rajendra Pradeepa, Mohan Deepa, Coimbatore Subramaniam Shanthirani, Raj Deepa, Viswanathan Mohan
Journal: Diabetes Care (2007)

OBJECTIVE—The aim of this study was to determine the prevalence of diabetic nephropathy among urban Asian-Indian type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—Type 2 diabetic subjects (n = 1,716), inclusive of known diabetic subjects (KD subjects) (1,363 of 1,529; response rate 89.1%) and randomly selected newly diagnosed diabetic subjects (NDD subjects) (n = 353) were selected from the Chennai Urban Rural Epidemiology Study (CURES). Microalbuminuria was estimated by immunoturbidometric assay and diagnosed if albumin excretion was between 30 and 299 μg/mg of creatinine, and overt nephropathy was diagnosed if albumin excretion was ≥300 μg/mg of creatinine in the presence of diabetic retinopathy, which was assessed by stereoscopic retinal color photography. RESULTS—The prevalence of overt nephropathy was 2.2% (95% CI 1.51–2.91). Microalbuminuria was present in 26.9% (24.8–28.9). Compared with the NDD subjects, KD subjects had greater prevalence rates of both microalbuminuria with retinopathy and overt nephropathy (8.4 vs. 1.4%, P &amp;lt; 0.001; and 2.6 vs. 0.8%, P = 0.043, respectively). Logistic regression analysis showed that A1C (odds ratio 1.325 [95% CI 1.256–1.399], P &amp;lt; 0.001), smoking (odds ratio 1.464, P = 0.011), duration of diabetes (1.023, P = 0.046), systolic blood pressure (1.020, P &amp;lt; 0.001), and diastolic blood pressure (1.016, P = 0.022) were associated with microalbuminuria. A1C (1.483, P &amp;lt; 0.0001), duration of diabetes (1.073, P = 0.003), and systolic blood pressure (1.031, P = 0.004) were associated with overt nephropathy. CONCLUSIONS—The results of the study suggest that in urban Asian Indians, the prevalence of overt nephropathy and microalbuminuria was 2.2 and 26.9%, respectively. Duration of diabetes, A1C, and systolic blood pressure were the common risk factors for overt nephropathy and microalbuminuria.
Processing limitations can help neural growth build hierarchical representations
Authors: Gary Haith
Journal: Behavioral and Brain Sciences (1997)

Processing limitations can be an advantage for a learner (Elman 1993; Newport 1990; Turkewitz 1982). They can filter input to the learner so that the relations to be learned increase in complexity only gradually. The time-course of filtered input can complement the growing neural representations discussed by Quartz &amp; Sejnowski.
Second messenger systems and adaptation.
Authors: F S Gorelick
Journal: Gut (1987)

Adaptive changes represent shifts in the equilibrium state of biologic systems in reponse to long standing alterations in their surrounding environment.Adap- tation encompasses a variety of cellular changes ranging from very specific responses, such as variation in the production of a single protein, to broader responses including alterations in the rate of cell growth.It is certain that the effectors for adaptive responses involve a complex and multilevel cellular network.As indicated by Figure 1, it can be anticipated that these effectors will include various ligands and their receptors, signal transduction pathways, and transcriptional and translational mech- anisms.Our current understanding of each of these components is growing, and warrants a consideration of potential mechanisms whereby the signals for adaptive responses may be transmitted to their intracellular targets.Adaptation appears to be governed by two general types of transduction mechanisms.The first acts through the modulation of traditional second messenger pathways known to be directed by calcium, lipids, and cyclic nucleotides.A second type of Signal Receptor * Transduction Adaptive response Transcription Translation Fig. 1Schematic representation of the sequence of events which result in an adaptive response.In some systems, the transduction elements may directly act on translational events to effect an adaptive response.
Discrepancy between plasma and lung angiotensin-converting enzyme activity in experimental congestive heart failure. A novel aspect of endothelium dysfunction.
Authors: H Huang, J F Arnal, C Llorens-Cortes, M Challah, F Alhenc-Gelas, P Corvol, J B Michel
Journal: Circulation Research (1994)

The renin-angiotensin and cardiac natriuretic systems play an important role in the pathophysiology of congestive heart failure (CHF). The status of the membrane-bound pulmonary and renal activities of three ectoenzymes involved in the regulation of these systems-angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP), and aminopeptidase A (APA)-was investigated in Wistar rats 3 months after induction of myocardial infarction (MI) and in sham-operated (control) rats. Plasma renin activity and ACE activity, plasma angiotensin II (Ang II) levels, and atrial natriuretic factor levels were simultaneously determined. The lung ACE activity was decreased in MI rats compared with control rats (P &lt; .0001), and this decrease depended on the severity of the heart failure. In contrast, plasma ACE activity was increased in MI rats (P &lt; .01), and this increase was also proportional to the severity of MI. Northern blot analysis showed that the lung ACE mRNA level in severe MI rats was half that of the control rats. Renal ACE activity of the MI rats was not affected, and neither renal or pulmonary NEP nor pulmonary APA activities were altered. Thus, lung ACE gene expression appears to be both organ- and enzyme-specifically regulated during CHF. Whereas plasma renin was increased in heart failure rats, plasma Ang II levels were not different from those of control rats. Thus, decreased lung ACE activity could possibly contribute to keeping plasma Ang II levels in the normal range. The decrease in lung ACE activity and mRNA levels, combined with increased plasma ACE activity, represents a novel aspect of endothelial dysfunction in CHF.(ABSTRACT TRUNCATED AT 250 WORDS)
Knockdown of Fibronectin Induces Mitochondria-Dependent Apoptosis in Rat Mesangial Cells
Authors: Di Wu, XiangMei Chen, DengFu Guo, Quan Hong, Bo Fu, Rui Ding, LiFang Yu, Kai Hou, Zhe Feng, XiaoJie Zhang, JianZhong Wang
Journal: Journal of the American Society of Nephrology (2005)

Extracellular matrix (ECM) expansion and mesangial cell (MC) proliferation are prominent features of most types of glomerulosclerosis. A delicate balance between the ECM and MC regulates cell survival. Increasing evidence shows that a loss of ECM components can cause mitochondrial dysfunction and induce cell apoptosis. It is proposed that directly blocking the synthesis of ECM components could lighten ECM accumulation and suppress cell overproliferation status. Fibronectin, one of the predominant adhesive glycoproteins of the mesangial ECM, provides the survival signal for cells. Its accumulation can be observed in most types of glomerulosclerosis. In this study, angiotensin II–induced fibronectin was suppressed by an RNA interference technique. It is interesting that MC slowly underwent apoptosis after infection with a retrovirus that continuously suppressed fibronectin synthesis. It was found that MC apoptosis occurred in a mitochondria-dependent manner mainly as a result of cytochrome c release and downstream caspase-3 and -9 activation. Furthermore, it was demonstrated that fibronectin knockdown affected mitochondrial handling of Ca2+ release from the endoplasmic reticulum. Importantly, blocking the inositol 1,4,5-triphosphate receptor with, 3,4,5-trimethoxybenzoate or decreasing Ca2+ in the ECM with EGTA partially saved the cells from apoptosis. These studies, which explored a new method for simultaneously inhibiting MC proliferation and ECM accumulation, may represent a novel therapeutic approach to glomerulosclerosis.
Future of Cancer Incidence in the United States: Burdens Upon an Aging, Changing Nation
Authors: Benjamin D. Smith, Grace L. Smith, Arti Hurria, Gabriel N. Hortobagyi, Thomas A. Buchholz
Journal: Journal of Clinical Oncology (2009)

By 2030, the United States' population will increase to approximately 365 million, including 72 million older adults (age > or = 65 years) and 157 million minority individuals. Although cancer incidence varies by age and race, the impact of demographic changes on cancer incidence has not been fully characterized. We sought to estimate the number of cancer patients diagnosed in the United States through 2030 by age and race.Current demographic-specific cancer incidence rates were calculated using the Surveillance Epidemiology and End Results database. Population projections from the Census Bureau were used to project future cancer incidence through 2030.From 2010 to 2030, the total projected cancer incidence will increase by approximately 45%, from 1.6 million in 2010 to 2.3 million in 2030. This increase is driven by cancer diagnosed in older adults and minorities. A 67% increase in cancer incidence is anticipated for older adults, compared with an 11% increase for younger adults. A 99% increase is anticipated for minorities, compared with a 31% increase for whites. From 2010 to 2030, the percentage of all cancers diagnosed in older adults will increase from 61% to 70%, and the percentage of all cancers diagnosed in minorities will increase from 21% to 28%.Demographic changes in the United States will result in a marked increase in the number of cancer diagnoses over the next 20 years. Continued efforts are needed to improve cancer care for older adults and minorities.
Quantitative influence of antibody and complement coating of red cells on monocyte-mediated cell lysis.
Authors: R J Kurlander, W F Rosse, G L Logue
Journal: Journal of Clinical Investigation (1978)

Monocyte-mediated lysis in vitro of human red cells coated with measured amounts of immunoglobulin G (IgG) or complement were studied. 1,000-1,500 molecules of IgG anti-D are necessary to effect measurable lysis, and lysis increases linearly with increasing levels of antibody sensitization. 100 microgram/ml of IgG1 abolished lysis even at maximal levels of anti-D sensitization (15,000 molecules/cell). Two isoimmune IgG anti-A or anti-B antisera were 5 to 10-fold less efficient in promoting phagocytosis or lysis per molecule of IgG bound; however, because of the greater antigen density of A or B, more than 100,000 molecules IgG/cell could be bound, producing equivalent lysis to anti-D-coated cells. Although inhibition by IgG1 was similar at equivalent levels of sensitization with anti-A, anti-B, or anti-D at high levels of coating with anti-A or anti-B (not attainable with anti-D), lysis was not inhibited by IgG1. Cells coated with human complement components alone were not lysed by monocytes; however, complement coating augmented IgG-mediated lysis and reduced the quantity of anti-D necessary to produce lysis to less than 1,000 molecules/cell. After thorough degradation of C3b by serum to C3d, complement augmentation persisted.
Production of Lupus Erythematosus (L.E.) Cells in the Dog by the Transfusion of Systemic Lupus Erythematosus Plasma
Authors: G. Bencze, M. Ludanyi
Journal: Annals of the Rheumatic Diseases (1960)

The production of the lupus erythematosus cell phenomenon by the transfusion of lupus erythematosus plasma in three patients with malignant disease was the subject of an earlier report (Bencze, Cserhati, Kovacs, and Tiboldi, 1958). Numerous unsuccessful attempts have been made to produce L.E. cells in animals. The present paper reports the results of systemic lupus erythematosus (S.L.E.) plasma transfusion in six dogs, a seventh dog being used as a control.
Hope, Hype and Help: Ethically Assessing the Growing Market in Stem Cell Therapies
Authors: Arthur Caplan, Bruce Levine
Journal: The American Journal of Bioethics (2010)

"Hope, Hype and Help: Ethically Assessing the Growing Market in Stem Cell Therapies." The American Journal of Bioethics, 10(5), pp. 24–25 Bruce Levine is a member of the International Society for Cellular Therapy and the American Society of Gene and Cell Therapy.
Neuroimaging in the early diagnosis of neurodegenerative disease
Authors: A Jon Stoessl
Journal: Translational Neurodegeneration (2012)

Functional imaging may be useful for both the early diagnosis as well as preclinical detection of neurodegenerative disease. Additionally, while structural imaging has traditionally been regarded as a tool to exclude alternate diagnoses, recent advances in magnetic resonance show promise for greater diagnostic specificity. The role of MR and radionuclide imaging in early diagnosis and preclinical detection of dementia and parkinsonism are reviewed here.
SOCIAL AND WORK ADJUSTMENT IN PATIENTS WITH EPILEPSY
Authors: MARGARET A. LENNOX, JENNIE MOHR
Journal: American Journal of Psychiatry (1950)

1. Twenty-two unselected male clinic epileptic patients, ages 20-52, were studied with reference to social, work, school, and marital adjustment. The interrelationships between adjustability and medical and psychological factors are presented. 2. In these patients medical handicap is greatest when seizures start before the age of 19, are frequent, are of the psychomotor variety, and respond poorly to treatment. 3. Work adjustment is better for patients whose medical handicap is marked. Social and school adjustment is better when the medical handicap is slight. Work and social adjustment is facilitated when the patients are able to accept their illness and to behave independently. 4. Eight of the 22 patients are married, and two marriages have ended in divorce. 5. Fewer families than patients are able to accept the illness, but almost all patients from accepting families are able to accept epilepsy realistically. Acknowledgment: We wish to acknowledge the assistance of Miss Irmgaard Rosensweig, who tabulated the data.
<i>In Vivo</i> Assessment of Arsenic Bioavailability in Rice and Its Significance for Human Health Risk Assessment
Authors: Albert L. Juhasz, Euan Smith, John Weber, Matthew Rees, Allan Rofe, Tim Kuchel, Lloyd Sansom, Ravi Naidu
Journal: Environmental Health Perspectives (2006)

Millions of people worldwide consume arsenic-contaminated rice; however, little is known about the uptake and bioavailability of arsenic species after arsenic-contaminated rice ingestion.In this study, we assessed arsenic speciation in greenhouse-grown and supermarket-bought rice, and determined arsenic bioavailability in cooked rice using an in vivo swine model.In supermarket-bought rice, arsenic was present entirely in the inorganic form compared to greenhouse-grown rice (using irrigation water contaminated with sodium arsenate), where most (approximately 86%) arsenic was present as dimethylarsinic acid (organic arsenic). Because of the low absolute bioavailability of dimethylarsinic acid and the high proportion of dimethylarsinic acid in greenhouse-grown rice, only 33 +/- 3% (mean +/- SD) of the total rice-bound arsenic was bioavailable. Conversely, in supermarket-bought rice cooked in water contaminated with sodium arsenate, arsenic was present entirely in the inorganic form, and bioavailability was high (89 +/- 9%).These results indicate that arsenic bioavailability in rice is highly dependent on arsenic speciation, which in turn can vary depending on rice cultivar, arsenic in irrigation water, and the presence and nature of arsenic speciation in cooking water. Arsenic speciation and bioavailability are therefore critical parameters for reducing uncertainties when estimating exposure from the consumption of rice grown and cooked using arsenic-contaminated water.
Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial
Authors: Roman Hovorka, Janet M Allen, Daniela Elleri, Ludovic J Chassin, Julie Harris, Dongyuan Xing, Craig Kollman, Tomas Hovorka, Anne Mette F Larsen, Marianna Nodale, Alessandra De Palma, Malgorzata E Wilinska, Carlo L Acerini, David B Dunger
Journal: The Lancet (2010)
Stromal Derived Factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis
Authors: Judong Pan, Javier Mestas, Marie D Burdick, Roderick J Phillips, George V Thomas, Karen Reckamp, John A Belperio, Robert M Strieter
Journal: Molecular Cancer (2006)

Abstract Renal cell carcinoma (RCC) is characterized by organ-specific metastases. The chemokine stromal derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 have been suggested to regulate organ-specific metastasis in various other cancers. On this basis, we hypothesized that the biological axis of CXCL12 via interaction with its receptor, CXCR4, is a major mechanism for RCC metastasis. We demonstrated that CXCR4 was significantly expressed on circulating cytokeratin+ RCC cells from patients with known metastatic RCC. We detected up-regulation of CXCR4 mRNA and protein levels on a human RCC cell line by either knockdown of the von Hippel-Lindau (VHL) tumor suppressor protein, or incubating the cells under hypoxic conditions. The enhanced CXCR4 expression was mediated through the interaction of the Hypoxia Inducible Factor-1α (HIF-1α) with the promoter region of the CXCR4 gene. Furthermore, the expression of CXCR4 on human RCC directly correlated with their metastatic ability in vivo in both heterotopic and orthotopic SCID mouse models of human RCC. Neutralization of CXCL12 in SCID mice abrogated metastasis of RCC to target organs expressing high levels of CXCL12; without altering tumor cell proliferation, apoptosis, or tumor-associated angiogenesis. Therefore, our data suggest that the CXCL12/CXCR4 biological axis plays an important role in regulating the organ-specific metastasis of RCC.
Expression of Tie2 and Ang-1 is related to the development of persistent and erosive disease in patients with early arthritis
Authors: M G H van de Sande, D de Launay, S Krausz, G P M van de Sande, C A Wijbrandts, P P Tak, K A Reedquist
Journal: Annals of the Rheumatic Diseases (2010)

Angiogenic growth factors Ang-1 and Ang-2 and their receptor Tie2 are expressed in inflamed synovial tissue and thought to contribute to disease initiation and joint destruction in rheumatoid arthritis (RA). The goal of this study was to examine the predictive value of synovial Ang-1 and Ang-2 expression and Tie2 activation with regard to disease outcome and erosive disease progression in disease-modifying anitrheumatic drug (DMARD)-naive patients with early …