tbuckley/cabot-search huggingface dataset:
Reassessing Epithelial to Mesenchymal Transition as a Prerequisite for Carcinoma Invasion and Metastasis
Authors: Jason J. Christiansen, Ayyappan K. Rajasekaran
Journal: Cancer Research (2006)

Abstract For most carcinomas, progression toward malignancy is accompanied by loss of epithelial differentiation and a shift towards a mesenchymal phenotype. This process, referred to as epithelial to mesenchymal transition (EMT), exacerbates motility and invasiveness of many cell types and is often considered a prerequisite for tumor infiltration and metastasis. However, there are numerous examples of advanced carcinomas that adopt some mesenchymal features, yet retain characteristics of well-differentiated epithelial cells. We provide a review of these reports and describe mechanisms to explain the morphologic and molecular heterogeneity and plasticity of malignant carcinoma cells, including incomplete EMT, reversion to an epithelial phenotype, and collective migration. We suggest that these mechanisms can manifest in a series of independent and reversible steps and that EMT represents just one mechanism in the global metastatic carcinoma development process. (Cancer Res 2006; 66(17): 8319-26)
Chronic Immune Thrombocytopenic Purpura in Monozygotic Twins
Authors: Andrew J. Laster, C. Lockard Conley, Thomas S. Kickler, Carole A. Dorsch, Wilma B. Bias
Journal: New England Journal of Medicine (1982)

Chronic immune thrombocytopenic purpura (ITP) appeared in monozygotic twin girls during adolescence. An older sister was discovered to have less severe thrombocytopenia without purpura. Increased amounts of platelet-associated immunoglobulin were detected in the proband and her sisters but in no other members of the family. Antibodies reacting with nuclear components were demonstrated in the serum of the three sisters, both parents, and other members of the kindred, some of whom had immunologically mediated clinical disorders. These observations add to the increasing evidence that a genetically determined disorder of immune regulation is often a factor predisposing to chronic ITP.The Kindred . . .
Carpal Tunnel Syndrome and Hemodialysis
Authors: Stanley F. Wainapel
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The recent article by Jain et al (242:2868, 1979), "Carpal Tunnel Syndrome in Patients Undergoing Maintenance Hemodialysis," prompts the following observations. Although distal motor latency (DML) was measured in median and ulnar nerves, the distal sensory latency (DSL) in these nerves was either not performed or not recorded. Since the median nerve DSL is known to be a far more sensitive indicator of carpal tunnel syndrome than the DML,<sup>1</sup>the reported incidence of the syndrome (ten of 62 hemodialysis patients) is probably a spuriously low one. Carpal tunnel syndrome is more frequently encountered in patients with systemic conditions associated with peripheral polyneuropathy such as diabetes mellitus and rheumatoid arthritis. Also among these are acute and chronic renal failure.<sup>2</sup>Perhaps the carpal tunnel syndrome found in all these systemic conditions can be partly ascribed to heightened sensitivity of a neuropathic median nerve to relatively minor degrees
Abstract 4160: Glycoprotein biomarkers for bladder cancer detection identified using LC-MS/MS and label free quantification
Authors: Steven Goodison, Na Yang, Xiaolei Xie, Yashu Liu, Virginia Urquidi, Charles J. Rosser, David Lubman
Journal: Cancer Research (2011)

Abstract PURPOSE: Cancers of the urinary bladder are the fifth most commonly diagnosed malignancy in the US. Early clinical diagnosis of bladder cancer remains a major challenge and the development of noninvasive methods for detection and surveillance is desirable for both patients and health care providers. METHODS: In order to identify urinary proteins with potential clinical utility we enriched and profiled the glycoprotein component of urine samples using a dual-lectin affinity chromatography and LC-MS/MS platform. RESULTS: From a primary sample set obtained from 56 cancer patients and 47 healthy individuals, a total of 265 distinct glycoproteins were identified with high confidence, and changes in glycoprotein abundance between groups were quantified by a label-free spectral counting method. Validation of candidate biomarker disease association was performed on second set of 70 independent samples using an antibody-lectin sandwich microarray and ELISA. Increased levels of urinary alpha-1-antitrypsin (A1AT) glycoprotein were identified and confirmed as being indicative of the presence of bladder cancer (p value &amp;lt; 0.0001). CONCLUSION: The described strategy can be used to discover biomarkers for disease status in other body fluids. Application of the strategy in this study has provided novel candidate biomarkers for the non-invasive molecular detection of bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4160. doi:10.1158/1538-7445.AM2011-4160
Aldehyde Dehydrogenase–Expressing Colon Stem Cells Contribute to Tumorigenesis in the Transition from Colitis to Cancer
Authors: Joseph E. Carpentino, Mark J. Hynes, Henry D. Appelman, Tong Zheng, Dennis A. Steindler, Edward W. Scott, Emina H. Huang
Journal: Cancer Research (2009)

Abstract Patients with chronic ulcerative colitis are at increased risk of developing colorectal cancer. Although current hypotheses suggest that sporadic colorectal cancer is due to inability to control cancer stem cells, the cancer stem cell hypothesis has not yet been validated in colitis-associated cancer. Furthermore, the identification of the colitis to cancer transition is challenging. We recently showed that epithelial cells with the increased expression of aldehyde dehydrogenase in sporadic colon cancer correlate closely with tumor-initiating ability. We sought to determine whether ALDH can be used as a marker to isolate tumor-initiating populations from patients with chronic ulcerative colitis. We used fluorescence-activated cell sorting to identify precursor colon cancer stem cells from colitis patients and report both their transition to cancerous stem cells in xenografting studies as well as their ability to generate spheres in vitro. Similar to sporadic colon cancer, these colitis-derived tumors were capable of propagation as sphere cultures. However, unlike the origins of sporadic colon cancer, the primary colitic tissues did not express any histologic evidence of dysplasia. To elucidate a potential mechanism for our findings, we compared the stroma of these different environments and determined that at least one paracrine factor is up-regulated in the inflammatory and malignant stroma compared with resting, normal stroma. These data link colitis and cancer identifying potential tumor-initiating cells from colitic patients, suggesting that sphere and/or xenograft formation will be useful to survey colitic patients at risk of developing cancer. [Cancer Res 2009;69(20):8208–15]
Endoscopic Gallstone Extraction Following Hydrostatic Balloon Dilatation of Stricture in the Common Bile Duct
Authors: R. Stave, M. Osnes
Journal: Endoscopy (1985)

A patient with long-standing biliary complaints and a previous cholecystojejunostomy, reputed to be suffering from primary biliary cirrhosis was, on endoscopic retrograde cholangiography (ERC), found to have several large gallstones proximal to a stenosis in the common bile duct.
Backache and the Guillain-Barre syndrome: a diagnostic problem.
Authors: J E Clague, R R Macmillan
Journal: BMJ (1986)

A propos de 2 observations de syndrome de Guillain-Barre ou des douleurs dorsales ont precede toute autre manifestation. Des explorations neurologiques completes et un examen du LCR seraient utiles pour faire le diagnostic precocement et pour bien conduire le traitement
Evaluation (not validation) of quantitative models.
Authors: N Oreskes
Journal: Environmental Health Perspectives (1998)

The present regulatory climate has led to increasing demands for scientists to attest to the predictive reliability of numerical simulation models used to help set public policy, a process frequently referred to as model validation. But while model validation may reveal useful information, this paper argues that it is not possible to demonstrate the predictive reliability of any model of a complex natural system in advance of its actual use. All models embed uncertainties, and these uncertainties can and frequently do undermine predictive reliability. In the case of lead in the environment, we may categorize model uncertainties as theoretical, empirical, parametrical, and temporal. Theoretical uncertainties are aspects of the system that are not fully understood, such as the biokinetic pathways of lead metabolism. Empirical uncertainties are aspects of the system that are difficult (or impossible) to measure, such as actual lead ingestion by an individual child. Parametrical uncertainties arise when complexities in the system are simplified to provide manageable model input, such as representing longitudinal lead exposure by cross-sectional measurements. Temporal uncertainties arise from the assumption that systems are stable in time. A model may also be conceptually flawed. The Ptolemaic system of astronomy is a historical example of a model that was empirically adequate but based on a wrong conceptualization. Yet had it been computerized--and had the word then existed--its users would have had every right to call it validated. Thus, rather than talking about strategies for validation, we should be talking about means of evaluation. That is not to say that language alone will solve our problems or that the problems of model evaluation are primarily linguistic. The uncertainties inherent in large, complex models will not go away simply because we change the way we talk about them. But this is precisely the point: calling a model validated does not make it valid. Modelers and policymakers must continue to work toward finding effective ways to evaluate and judge the quality of their models, and to develop appropriate terminology to communicate these judgments to the public whose health and safety may be at stake.
Mechanism of unresponsiveness to the alpha 1-6 epitope of dextran B512 in a C57BL substrain.
Authors: C Fernandez, G Möller
Journal: The Journal of Experimental Medicine (1983)

C57BL/10ScCr mice are low responders to the alpha 1-6 epitope of dextran B512, although other C57BL mice are high responders. Both thymus-independent and thymus-dependent forms of dextran failed to induce an immune response in C57BL/10ScCr mice, but dextran functioned as a good carrier for antihapten responses in this strain. Dextran is a potent polyclonal B cell activator for cells from C57BL/10ScCr mice, although such cells are not activated by LPS. The C57BL/10ScCr mice possess the Igh-V gene coding for antibodies against dextran and the antidextran antibodies induced in (A X C57BL/10ScCr)F1 hybrids share an idiotype with antidextran antibodies produced in C57BL/10 mice. Bone marrow cells from C57BL/10ScCr mice do not respond to dextran when transferred into lethally irradiated C57BL/10 mice and C57BL/10 cells transferred into C57BL/10ScCr mice give a strong antidextran response. Thus, B cells having both the Igh-V gene coding for antibodies against dextran and activation receptors for dextran cannot be activated into antibody synthesis against any form of this immunogen. This determinant specific immunodeficiency suggests the existence of as yet unknown regulatory influences on Igh-V gene expression or B cell activation.
EXPERIMENTAL RICKETS IN RATS
Authors: Alwin M. Pappenheimer
Journal: The Journal of Experimental Medicine (1922)

Rats which had developed rickets were treated with cod liver oil or an active fraction of cod liver oil, and the various changes which occur in the healing of the bone lesions were studied. Several phases are described, from the early deposit of calcium salts in the zone of preparatory calcification to the return to normal bone. These stages correspond closely to those found in the healing of human rickets.
Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean populations
Authors: Daiki Miki, Michiaki Kubo, Atsushi Takahashi, Kyong Ah Yoon, Jeongseon Kim, Geon Kook Lee, Jae Ill Zo, Jin Soo Lee, Naoya Hosono, Takashi Morizono, Tatsuhiko Tsunoda, Naoyuki Kamatani, Kazuaki Chayama, Takashi Takahashi, Johji Inazawa, Yusuke Nakamura, Yataro Daigo
Journal: Nature Genetics (2010)
Treatment with atorvastatin ameliorates hepatic very[ndash ]low-density lipoprotein overproduction in an animal model of insulin resistance, the fructose-fed Syrian golden hamster: Evidence that reduced hypertriglyceridemia is accompanied by improved hepatic insulin sensitivity
Authors: Leyla Mangaloglu, Raphael C. Cheung, Stephen C. Van Iderstine, Changiz Taghibiglou, Louisa Pontrelli, Khosrow Adeli
Journal: Metabolism (2002)
Kidney Depth Measurement and Its Influence on Quantitation of Function from Gamma Camera Renography
Authors: S M GRUENEWALD, L T COLLINS, R M FAWDRY
Journal: Clinical Nuclear Medicine (1985)

Both total and relative renal function assessed from gamma camera renography are influenced by the depths of the kidneys in the body. Despite the ease with which renal depths may be measured (by ultrasound or nuclear medicine lateral scans), when calculating the total uptake function it is common practice to estimate the renal depth from the patient's weight-to-height ratio. Furthermore, it is often assumed that there is no significant effect on relative function measurements due to different depths of right and left kidneys. Our data, from 150 consecutive patients, does not support this assumption or the use of calculated depth estimates and highlights the need for accurate kidney depth measurement.
Decline in mortality from coronary heart disease in Finland from 1969 to 1979.
Authors: J T Salonen, P Puska, T E Kottke, J Tuomilehto, A Nissinen
Journal: BMJ (1983)

The trends in mortality from coronary heart disease in the 1970s and the differences in trends between counties within Finland were calculated from official mortality statistics among the population aged 35 to 64 years. During this period coronary mortality declined by a mean of 1.1% for men and 2.3% for women annually in the whole of Finland. A community based cardiovascular control programme was started in 1972 in North Karelia, a county in the east of Finland. The decline in coronary mortality in this county between 1969 and 1979 was 24% in men and 51% in women. The decline in the rest of Finland over the same period was 12% in men and 24% in women. The decline in North Karelia was greater than that in other counties of Finland for both men and women and that difference exceeded random variation, with over 95% likelihood for both sexes. Even with adjustment for rates before 1974 with cross-county multiple regression analyses the difference persisted. Although further studies are needed, the changes in coronary mortality in North Karelia suggest that the preventive programme has been effective.
Cleft palate: players, pathways, and pursuits
Authors: Jeffrey C. Murray, Brian C. Schutte
Journal: Journal of Clinical Investigation (2004)

Cleft lip and palate is a common human birth defect, and its causes are being dissected through studies of human populations and through the use of animal models. Mouse models in particular have made a substantial contribution to our understanding of the gene pathways involved in palate development and the nature of signaling molecules that act in a tissue-specific manner at critical stages of embryogenesis. Related work has provided further support for investigating the role of common environmental triggers as causal covariates.
Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia
Authors: Kensuke Kojima, Marina Konopleva, Twee Tsao, Hideki Nakakuma, Michael Andreeff
Journal: Blood (2008)
Vital role of the itch-scratch response in development of spontaneous dermatitis in NC/Nga mice
Authors: K. Mihara, K. Kuratani, T. Matsui, M. Nakamura, K. Yokota
Journal: British Journal of Dermatology (2004)

The itch sensation and the resultant response, scratching, are important symptoms of atopic dermatitis (AD) and have a significant impact on the quality of life of affected patients. However, the influence of the itch-scratch response on the pathology of AD has not been precisely elucidated.To investigate the role of scratching behaviour in the development of spontaneous dermatitis using conventionally raised NC/Nga mice (Conv-NC mice), which are known to be an animal model for human AD.Capsaicin-sensitive sensory nerves of the mice were ablated by neonatal capsaicin treatment (Cap-NC mice), and the development of spontaneous dermatitis in the Cap-NC mice was compared chronologically with that in Conv-NC mice.Scratching behaviour was almost completely prevented in Cap-NC mice raised for 84 days under conventional conditions, and the development of dermatitis and elevation of the serum IgE level were significantly suppressed. Histological analysis revealed that the numbers of infiltrating eosinophils and mast cells in the lesional skin of Cap-NC mice were lower than those in Conv-NC mice. Immunological studies showed that the capability of spleen T cells to produce both T-helper (Th) 1 (interferon-gamma) and Th2 [interleukin (IL)-5 and IL-13] cytokines was diminished in Cap-NC mice. Furthermore, serum levels of IL-18 were approximately twice higher in Conv-NC mice than in Cap-NC mice.These observations suggest that scratching behaviour contributes to the development of dermatitis by enhancing various immunological responses in the murine AD model, implying that prevention of the itch sensation and/or itch-associated scratching behaviour is an effective treatment for AD.
Circulating immune complexes and disease activity in Crohn's disease.
Authors: R Fiasse, A Z Lurhuma, C L Cambiaso, P L Masson, C Dive
Journal: Gut (1978)

Circulating immune complexes were determined in 59 consecutive patients with Crohn9s disease and 100 blood donors by a double method based on the inhibition of the agglutinating activity of CIq and/or rheumatoid factor on the IgG-coated polystyrene particles. In patients, the incidence of positive immune complexes was 63% and 61% at first testing, 85% and 78% at subsequent determinations; there was a good correlation between the inhibition titres of CIq and those of rheumatoid factor (p less than 0.001). In blood donors, the incidence was 22% and 14% at low titre. The incidence of immune complexes was the lowest (36%) in the group of resected patients without signs of relapse; repeat determinations showed absence of immune complexes three months postoperatively. In patients medically treated for primary disease or relapse, rheumatoid factor titre higher than 1/1 was less frequent than in medically untreated patients with active disease (p less than 0.01). A significantly higher concentration of serum alpha-1-antitrypsin and orosomucoid, and a significantly lower level of serum iron were found in patients with an IC titre exceeding 1/1; longitudinal studies showed in most cases a concordance between the evolution of immune complex titres, inflammatory parameters and clinical status.
Everolimus in Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: Gerd Walz, Klemens Budde, Marwan Mannaa, Jens Nürnberger, Christoph Wanner, Claudia Sommerer, Ulrich Kunzendorf, Bernhard Banas, Walter H. Hörl, Nicholas Obermüller, Wolfgang Arns, Hermann Pavenstädt, Jens Gaedeke, Martin Büchert, Christoph May, Harald Gschaidmeier, Stefan Kramer, Kai-Uwe Eckardt
Journal: New England Journal of Medicine (2010)

Autosomal dominant polycystic kidney disease (ADPKD) is a slowly progressive hereditary disorder that usually leads to end-stage renal disease. Although the underlying gene mutations were identified several years ago, efficacious therapy to curtail cyst growth and prevent renal failure is not available. Experimental and observational studies suggest that the mammalian target of rapamycin (mTOR) pathway plays a critical role in cyst growth.In this 2-year, double-blind trial, we randomly assigned 433 patients with ADPKD to receive either placebo or the mTOR inhibitor everolimus. The primary outcome was the change in total kidney volume, as measured on magnetic resonance imaging, at 12 and 24 months.Total kidney volume increased between baseline and 1 year by 102 ml in the everolimus group, versus 157 ml in the placebo group (P=0.02) and between baseline and 2 years by 230 ml and 301 ml, respectively (P=0.06). Cyst volume increased by 76 ml in the everolimus group and 98 ml in the placebo group after 1 year (P=0.27) and by 181 ml and 215 ml, respectively, after 2 years (P=0.28). Parenchymal volume increased by 26 ml in the everolimus group and 62 ml in the placebo group after 1 year (P=0.003) and by 56 ml and 93 ml, respectively, after 2 years (P=0.11). The mean decrement in the estimated glomerular filtration rate after 24 months was 8.9 ml per minute per 1.73 m2 of body-surface area in the everolimus group versus 7.7 ml per minute in the placebo group (P=0.15). Drug-specific adverse events were more common in the everolimus group; the rate of infection was similar in the two groups.Within the 2-year study period,as compared with placebo, everolimus slowed the increase in total kidney volume of patients with ADPKD but did not slow the progression of renal impairment [corrected]. (Funded by Novartis; EudraCT number, 2006-001485-16; ClinicalTrials.gov number, NCT00414440.)
Long-term responses of atrial rate and peripheral resistance to changes in ventricular pacing rate in awake dogs with atrioventricular block.
Authors: S J Fisher, A M Scher, C R Wyss
Journal: Circulation Research (1984)

We wished to see if a maintained change in pressure at the baroreceptors leads to a maintained or a transient change in heart rate and total peripheral resistance, and if long-term changes in rate and resistance paralleled one another. In awake dogs with intact baroreceptors and complete atrioventricular block, ventricular rate was held alternately at high (90 beats/min) and low (50 beats/min) levels, each for 2 days. This cycle was repeated several times. Data were recorded for 1.5 hours each day. With this change in ventricular rate, there was a maintained change over 2 days in arterial (14.4 +/- 1.0 mm Hg) and central venous (3.0 +/- 1.2 mm Hg) pressures. These changes in pressure were accompanied by a maintained change in atrial rate of 41.1 +/- 9.4 beats/min; peripheral resistance, however, changed only transiently. In three animals, the half-cycle length was 1 week. Changes in heart rate also persisted for this period. It appears from these studies that there is long-term control of heart rate, but not of peripheral resistance. Hypotheses to explain these results are presented.