tbuckley/cabot-search huggingface dataset:
Relative Contribution of Dietary Protein Level and Aflatoxin B&lt;sub&gt;1&lt;/sub&gt; Dose in Generation of Presumptive Preneoplastic Foci in Rat Liver&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: George E. Dunaif, T. Colin Campbell
 5
Journal: JNCI Journal of the National Cancer Institute (1987)

Male weanling F344 rats were orally gavaged with aflatoxin B1 (AFB1) in daily doses of 200, 235, 270, 300, and 350 micrograms/kg/day for a total of 10 doses over a 12-day period, and then 1 week after the last dose they were fed diets of varying protein (casein) content to compare the contribution of AFB1 dose and dietary protein level on the development of presumptive preneoplastic gamma-glutamyltransferase-positive (GGT+) foci in rat liver. All animals were fed the same 20% dietary casein level during the dosing period. One week after the end of the dosing period, one-half of the animals in each dose group were then continued on the 20% casein diet for the entire 12-week foci-development period; the remaining half in each dose group were fed lower levels of dietary casein during the foci-development period for the increasing AFB1 dose groups (20, 16, 12, 8, and 4% casein for the 235-, 250-, 270-, 300-, and 350-micrograms/kg/day groups, respectively). The AFB1 dose groups used were determined in a preliminary experiment. In this previous experiment, a clearly discernible threshold dose at about 100-150 micrograms AFB1/kg/day (below which no GGT+ foci were observed) and a steep slope between 150 and 400 micrograms/kg/day were produced. In the second experiment, while the expected positive slope of (AFB1) dose versus (GGT+ foci) response relationship was found for animals fed the 20% casein diet, the dose response for the animals fed the lower levels of casein was eliminated, providing evidence that nutrient intake during the postdosing foci development is more rate limiting toward the development of these preneoplastic lesions than is the carcinogen dose.
Hemodynamic, Renal, and Hormonal Effects of Adrenomedullin Infusion in Patients With Congestive Heart Failure
Authors: Noritoshi Nagaya, Toru Satoh, Toshio Nishikimi, Masaaki Uematsu, Shinichi Furuichi, Fumio Sakamaki, Hideo Oya, Shingo Kyotani, Norifumi Nakanishi, Yoichi Goto, Yoshiaki Masuda, Kunio Miyatake, Kenji Kangawa
Journal: Circulation (2000)

Background —Experimental studies have shown that adrenomedullin (AM) causes vasodilatation, diuresis, and a positive inotropic effect. In humans, however, whether infusion of AM has beneficial effects in congestive heart failure (CHF) remains unknown. Methods and Results —Hemodynamic, renal, and hormonal responses to intravenous infusion of human AM (0.05 μg · kg −1 · min −1 ) were examined in 7 patients with CHF and 7 normal healthy subjects (NL). In NL group, AM significantly decreased mean arterial pressure (−16 mm Hg, P &lt;0.05) and increased heart rate (+12 bpm, P &lt;0.05). In CHF group, AM also decreased mean arterial pressure (−8 mm Hg, P &lt;0.05) and increased heart rate (+5 bpm, P &lt;0.05), but to a much lesser degree ( P &lt;0.05 versus NL). AM markedly increased cardiac index (CHF, +49%; NL, +39%, P &lt;0.05) while decreasing pulmonary capillary wedge pressure (CHF, −4 mm Hg; NL, −2 mm Hg, P &lt;0.05). AM significantly decreased mean pulmonary arterial pressure only in CHF (−4 mm Hg, P &lt;0.05). AM increased urine volume (CHF, +48%; NL, +62%, P &lt;0.05) and urinary sodium excretion (CHF, +42%; NL, +75%, P &lt;0.05). Only in CHF, plasma aldosterone significantly decreased during (−28%, P &lt;0.05) and after (−36%, P &lt;0.05) AM infusion. These parameters remained unchanged in 7 patients with CHF and 6 healthy subjects who received placebo. Conclusions —Intravenous infusion of AM has beneficial hemodynamic and renal effects in patients with CHF.
DNA binding specificities of the long zinc-finger recombination protein PRDM9
Authors: Timothy Billings, Emil D Parvanov, Christopher L Baker, Michael Walker, Kenneth Paigen, Petko M Petkov
Journal: Genome biology (2013)

Abstract Background Meiotic recombination ensures proper segregation of homologous chromosomes and creates genetic variation. In many organisms, recombination occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 (PRDM9), a long-array zinc-finger and chromatin-modifier protein. Determining the rules governing the DNA binding of PRDM9 is a major issue in understanding how it functions. Results Mouse PRDM9 protein variants bind to hotspot DNA sequences in a manner that is specific for both PRDM9 and DNA haplotypes, and that in vitro binding parallels its in vivo biological activity. Examining four hotspots, three activated by Prdm9 Cst and one activated by Prdm9 Dom2 , we found that all binding sites required the full array of 11 or 12 contiguous fingers, depending on the allele, and that there was little sequence similarity between the binding sites of the three Prdm9 Cst activated hotspots. The binding specificity of each position in the Hlx1 binding site, activated by Prdm9 Cst , was tested by mutating each nucleotide to its three alternatives. The 31 positions along the binding site varied considerably in the ability of alternative bases to support binding, which also implicates a role for additional binding to the DNA phosphate backbone. Conclusions These results, which provide the first detailed mapping of PRDM9 binding to DNA and, to our knowledge, the most detailed analysis yet of DNA binding by a long zinc-finger array, make clear that the binding specificities of PRDM9, and possibly other long-array zinc-finger proteins, are unusually complex.
Trends in Energy Intakes by Type of Fast Food Restaurant Among US Children From 2003 to 2010
Authors: Colin D. Rehm, Adam Drewnowski
Journal: JAMA Pediatrics (2015)

bipolar disorder (Figure).Similarly, we observed considerable hospital-level variation, with appendectomy showing the least variation and bipolar disorder showing the greatest variation in direct admission rates.In models adjusting for patient and hospital characteristics and disease severity, direct admissions were associated with 5% to 31% lower costs than ED admissions.Discussion | Direct admissions represent approximately 1 in 4 unscheduled pediatric hospitalizations nationally, with characteristics of children admitted directly aligning with those more likely to have a medical home, including white race/ ethnicity and private health insurance coverage. 7 The substantial variation in direct admission practices across hospitals and conditions may be influenced by disparities in access to timely outpatient acute care as well as differences in hospitals' and referring physicians' capacities to facilitate admissions without ED involvement.While the differences in costs between direct and ED admissions were striking, we acknowledge that our findings may have been influenced by residual confounding and we were unable to draw definitive conclusions about quality, safety, and effectiveness.In addition, direct admission points of origin were not reflected in these analyses.Nevertheless, our results suggest that increasing access to direction admissions may be a means to reduce ED volumes and health care costs.To accomplish this, research is needed to better understand key stakeholders' admission preferences, the drivers of these cost differences, and conditions and procedures best suited for this admission approach.
AN ENZYME IN MAST CELLS WITH PROPERTIES LIKE CHYMOTRYPSIN
Authors: Earl P. Benditt, Margaret Arase
Journal: The Journal of Experimental Medicine (1959)

Mast cells contain an enzyme which hydrolyzes 3-chloroacetoxy-2-naphthoic acid anilide. By using highly purified mast cells isolated by differential centrifugation in high density sucrose solutions we have been able to study this enzymatic activity in more detail. The enzyme has properties similar to those of chymotrypsin: Chymotrypsin will hydrolyze the histochemical substrate, and the chymotrypsin and mast cell activities with this substrate are similarly inhibited by diisopropylfluorophosphate. The mast cell enzyme is capable of hydrolyzing the N-acetyl esters of tryptophan, tyrosine, and phenylalanine, the relative rates of hydrolysis being similar to those seen with chymotrypsin. A characteristic trypsin substrate, p-toluenesulfonyl arginine methyl ester, is not acted upon by the mast cell enzyme or chymotrypsin. The pH activity curve of the new cell enzyme is similar to that of chymotrypsin as determined with N-acetyl-L-tryptophan ethyl ester as substrate.
Postoperative effects of neuromuscular exercise prior to hip or knee arthroplasty: a randomised controlled trial
Authors: Allan Villadsen, Søren Overgaard, Anders Holsgaard-Larsen, Robin Christensen, Ewa M Roos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To investigate the postoperative efficacy of a supervised programme of neuromuscular exercise prior to hip or knee arthroplasty. <h3>Methods</h3> In this assessor-blinded randomised controlled trial, we included 165 patients scheduled for hip or knee arthroplasty due to severe osteoarthritis (OA). An 8-week preoperative neuromuscular supervised exercise programme was delivered twice a week for 1 h as adjunct treatment to the standard arthroplasty procedure and compared with the standard arthroplasty procedure alone. The primary outcome was self-reported physical function measured on the activities of daily living (ADL) subscale in the Hip disability and Osteoarthritis Outcome Score (HOOS) and the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaires for patients with hip and knee OA, respectively. Primary endpoint was 3 months after surgery. <h3>Results</h3> 165 patients randomised to the two groups were on average 67±8 years, 84 (51%) had hip OA and 92 (56%) were women. 153 patients (93%) underwent planned surgery and were evaluated postoperatively. There was no statistically significant difference in effects between hip or knee patients (p=0.7370). Three months postoperatively, no difference was found between groups for ADL (4.4, 95% CI −0.8 to 9.5) or pain (4.5, 95% CI −0.8 to 9.9). However, there was a statistically significant difference indicating an effect of exercise over the entire period (baseline to 3-months postoperatively) (p=0.0029). <h3>Conclusions</h3> Eight weeks of supervised neuromuscular exercise prior to total joint arthroplasty (TJA) of the hip or knee did not confer additional benefits 3 months postoperatively compared with TJA alone. However, the intervention group experienced a statistically significant short-term benefit in ADL and pain, suggesting an earlier onset of postoperative recovery. <h3>Trial registration</h3> ClinicalTrials NCT01003756.
Cyclin D1/Cyclin-Dependent Kinase 4 Interacts with Filamin A and Affects the Migration and Invasion Potential of Breast Cancer Cells
Authors: Zhijiu Zhong, Wen-Shuz Yeow, Chunhua Zou, Richard Wassell, Chenguang Wang, Richard G. Pestell, Judy N. Quong, Andrew A. Quong
Journal: Cancer Research (2010)

Cyclin D1 belongs to a family of proteins that regulate progression through the G1-S phase of the cell cycle by binding to cyclin-dependent kinase (cdk)-4 to phosphorylate the retinoblastoma protein and release E2F transcription factors for progression through cell cycle. Several cancers, including breast, colon, and prostate, overexpress the cyclin D1 gene. However, the correlation of cyclin D1 overexpression with E2F target gene regulation or of cdk-dependent cyclin D1 activity with tumor development has not been identified. This suggests that the role of cyclin D1 in oncogenesis may be independent of its function as a cell cycle regulator. One such function is the role of cyclin D1 in cell adhesion and motility. Filamin A (FLNa), a member of the actin-binding filamin protein family, regulates signaling events involved in cell motility and invasion. FLNa has also been associated with a variety of cancers including lung cancer, prostate cancer, melanoma, human bladder cancer, and neuroblastoma. We hypothesized that elevated cyclin D1 facilitates motility in the invasive MDA-MB-231 breast cancer cell line. We show that MDA-MB-231 motility is affected by disturbing cyclin D1 levels or cyclin D1-cdk4/6 kinase activity. Using mass spectrometry, we find that cyclin D1 and FLNa coimmunoprecipitate and that lower levels of cyclin D1 are associated with decreased phosphorylation of FLNa at Ser2152 and Ser1459. We also identify many proteins related to cytoskeletal function, biomolecular synthesis, organelle biogenesis, and calcium regulation whose levels of expression change concomitant with decreased cell motility induced by decreased cyclin D1 and cyclin D1-cdk4/6 activities.
Altered miRNA Repertoire in the Simplified Chordate, Oikopleura dioica
Authors: X. Fu, M. Adamski, E. M. Thompson
Journal: Molecular Biology and Evolution (2008)

Recent studies reveal correlation between microRNA (miRNA) innovation and increased developmental complexity. This is exemplified by dramatic expansion of the miRNA inventory in vertebrates, a lineage where genome duplication has played a significant evolutionary role. Urochordates, the closest extant group to the vertebrates, exhibit an opposite trend to genome and morphological simplification. We show that the urochordate, larvacean, Oikopleura dioica, possesses the requisite miRNA biogenic machinery. The miRNAs isolated by small RNA cloning were expressed throughout the short life cycle, a number of which were stocked as maternal determinants prior to rapid embryonic development. We identify sex-specific miRNAs that appeared as male/female gonad differentiation became apparent and were maintained throughout spermatogenesis. Whereas 80% of mammalian miRNAs are hosted in introns of protein-coding genes, the majority of O. dioica miRNA loci were located in antisense orientations to such genes. Including sister group ascidians in analysis of the urochordate miRNA repertoire, we find that 11 highly conserved bilaterian miRNA families have been lost or derived to the point they are not recognizable in urochordates and a further 4 of these families are absent in larvaceans. Subsequent to this loss/derivation, at least 29 novel miRNA families have been acquired in larvaceans. This suggests a profound reorganization of the miRNA repertoire integral to evolution in the urochordate lineage.
High-Dose Chemotherapy With Reinfusion of Purged Autologous Bone Marrow Following Dose-Intense Induction as Initial Therapy for Metastatic Breast Cancer
Authors: M. J. Kennedy, R. A. Beveridge, S. D. Rowley, G. B. Gordon, M. D. Abeloff, N. E. Davidson
Journal: JNCI Journal of the National Cancer Institute (1991)

We assessed the toxicity and efficacy of high-dose chemotherapy consolidation with reinfusion of purged autologous bone marrow in women with metastatic breast cancer responding to a dose-intense outpatient regimen. Thirty women with hormone-unresponsive metastatic breast cancer, previously untreated with adjuvant doxorubicin or with any chemotherapy for metastatic disease, were treated with cyclophosphamide, methotrexate, doxorubicin, fluorouracil, vincristine, and leucovorin for 16 weeks. Twenty-four patients responded to therapy; 8 showed a complete response, and 16 showed a partial response. These patients proceeded to the next phase of the protocol, ie, marrow harvest and treatment with 6000 mg/m 2 cyclophosphamide and 800 mg/m 2 thiotepa given over 4 days. Harvested marrow was purged with 100 μg/mL 4-hydroperoxycyclophosphamide, and all patients engrafted satisfactorily. The predominant side effects were myelosuppressive and gastrointestinal, and there were no deaths from toxic effects. Three of the 16 patients who showed a partial response after the outpatient phase of treatment achieved a complete response after high-dose therapy. The partial response seen in two more patients converted to a complete response at all sites except bone. The median time to disease progression for all patients in this study was 13 months, and the median survival was 22 months. Four of the original 30 patients remained without disease progression a median of 27 months from entry into the study. This study indicates that this dose-intense regimen can be safely administered, even with the use of purged marrow, with an acceptable toxicity profile. This approach results in a high response rate in women with metastatic breast cancer and could form the basis for a regimen to be tested in the high-risk adjuvant setting. [J Natl Cancer Inst 83: 920–926, 1991]
Functional Interaction between Tumor Suppressor Menin and Activator of S-Phase Kinase
Authors: Robert W. Schnepp, Zhaoyuan Hou, Haoren Wang, Clark Petersen, Albert Silva, Hisao Masai, Xianxin Hua
Journal: Cancer Research (2004)

Abstract Multiple endocrine neoplasia type I (MEN1), a hereditary tumor syndrome, is characterized by the development of tumors in multiple endocrine organs. The gene mutated in MEN1 patients, Men1, encodes a tumor suppressor, menin. Overexpression of menin leads to inhibition of Ras-transformed cells. However, it is unclear whether menin is essential for repression of cell proliferation, and if it is, how it inhibits cell proliferation. Here, we show that targeted disruption of the Men1 gene leads to enhanced cell proliferation, whereas complementation of menin-null cells with menin reduces cell proliferation. Moreover, menin interacts with activator of S-phase kinase (ASK), a component of the Cdc7/ASK kinase complex that is crucial for cell proliferation, but does not appear to alter Cdc7 kinase activity in in vitro kinase assays. We identify the COOH terminus of menin as the domain that mediates the specific interaction with ASK. Notably, wild-type menin completely represses ASK-induced cell proliferation, although it does not obviously affect the steady-state cell cycle profile of ASK-infected cells. Interestingly, disease-related COOH-terminal menin mutants that do not interact with ASK completely fail to repress ASK-induced cell proliferation. Together, these findings demonstrate a functional link between menin and ASK in the regulation of cell proliferation.
Histochemical Evaluation of Canine Coronary Artery and Aortic Lesions Induced by Intravenous Allylamine
Authors: L. L. CONRAD, I. E. GONZALEZ, W. JOEL, R. H. FURMAN
Journal: Circulation Research (1956)

The early lesions of the coronary arteries and aorta in animals given intravenous allylamine are described and are noted to be characterized by glycogen accumulation and by ground substance change indicated by increased PAS-positive material present after incubation with diastase. It is suggested that heterogeneous polysaccharides and/or substances containing 1-2 glycol linkages, other than sulphated acid polysaccharides, may be of importance in the early lesion.
'Chronic duodenitis': a clinical pathological entity?
Authors: I T Beck, D S Kahn, M Lacerte, J Solymar, U Callegarini, M C Geokas
Journal: Gut (1965)

<h3>Objective:</h3> We sought to investigate incidence and trends of falls and Traumatic brain injury (TBI) in Alzheimer Disease (AD) cohort, and impact on mortality using a large administrative database <h3>Background:</h3> Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, with significant health-care burden. AD patients are more likely to fall and experience traumatic brain injury (TBI) than those without. However, there are no recent population based epidemiological studies to guide designing preventive strategies. <h3>Design/Methods:</h3> Hospitalizations with AD or TBI and age&gt;64 years were extracted from the Nationwide Inpatient Sample (NIS) 2006–2011. A subset of those with falls was identified using provided e-codes. Appropriate weights were attached to approximate national estimates. <h3>Results:</h3> Total hospitalizations from 2006–2011 was 62,949,73; out of which, 15.5% had AD with mean age = 83±7 years and 63.8% females, compared to mean age 78±8 and 56.3% females otherwise. TBI incidence in AD was 1.4% vs. 0.9% in non-AD (p&lt;0.0001). Fall incidence in AD was 11.5% vs. 6.7% in non-AD (p&lt;0.0001), and falls contributed to TBI in 68% cases. Fall incidence in AD increased from 10.5% (2006) to 12.1% (2011) (p&lt;0.0001). TBI incidence in AD with falls also increased from 7.7% (2006) to 10.0% (2011) (p&lt;0.0001). Overall in-hospital mortality was 4.7% in AD vs. 4.5% in non-AD (p&lt;0.0001). Mortality with TBI in AD was 6.9% vs. 4.7% in non-AD (p&lt;0.0001). In AD with falls cohort, mortality with TBI was 7.5% vs. 2.5% without TBI. <h3>Conclusions:</h3> There is a greater incidence of falls and TBI in AD compared to without AD, which is increasing yearly. Falls contribute to majority of TBI incidence in AD. TBI and falls also increase mortality incidence in AD. These findings necessitate investigation into their causes, impact on healthcare, and design of preventive strategies. <b>Disclosure:</b> Dr. Tahir has nothing to disclose. Dr. Al Jarrah has nothing to disclose. Dr. Khawaja has nothing to disclose. Dr. Izzy has nothing to disclose.
Histology of Some Neoplasms and Non-Neo-plastic Lesions Found in Wild Mice Maintained Under Laboratory Conditions
Authors: Thelma B. Dunn, Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1963)

The histology of some non-neoplastic conditions and spontaneous tumors found in a colony of wild house mice maintained at the National Cancer Institute has been described. Among the neoplasms were reticular neoplasms, a teratoid tumor from the side of the face, several ovarian tumors, a tumor from the foot pad, an osteogenic sarcoma, and a mast cell tumor. Interesting facts about these neoplasms were discussed. The reticular neoplasms were nearly all Type B (Hodgkin's-like lesion of the mouse). Lymphocytic neoplasms were rare, though readily induced by the leukemia-inducing Moloney virus. The teratoma appeared in a 10-week-old mouse and was located away from the midline. It was compared with a previously studied teratoma in the thigh of a noninbred Swiss mouse. The other neoplasms were compared with similar tumors in inbred mice. A non-neoplastic condition, retinal dystrophy, was found in 3 of 11 mice. This condition has been noted in all members of some inbred strains. Another anatomical difference between wild mice and laboratory mice was the absence in the wild mice of a cuboidal epithelial parietal lining of Bowman's capsule. This is a secondary sex characteristic that failed to appear in the wild mice even after testosterone treatment. A few other lesions and anomalies found also in laboratory mice were described.
Reversible Smad-Dependent Signaling between Tumor Suppression and Oncogenesis
Authors: Go Sekimoto, Koichi Matsuzaki, Katsunori Yoshida, Shigeo Mori, Miki Murata, Toshihito Seki, Hirofumi Matsui, Jun-ichi Fujisawa, Kazuichi Okazaki
Journal: Cancer Research (2007)

Abstract Cancer cells often gain advantage by reducing the tumor-suppressive activity of transforming growth factor-β (TGF-β) together with stimulation of its oncogenic activity as in Ras-transformed cells; however, molecular mechanisms remain largely unknown. TGF-β activates both its type I receptor (TβRI) and c-Jun NH2-terminal kinase (JNK), which phosphorylate Smad2 and Smad3 at the COOH-terminal (pSmad2/3C) and linker regions (pSmad2/3L). Here, we report that Ras transformation suppresses TβRI-mediated pSmad3C signaling, which involves growth inhibition by down-regulating c-Myc. Instead, hyperactive Ras constitutively stimulates JNK-mediated pSmad2/3L signaling, which fosters tumor invasion by up-regulating plasminogen activator inhibitor-1 and matrix metalloproteinase-1 (MMP-1), MMP-2, and MMP-9. Conversely, selective blockade of linker phosphorylation by a mutant Smad3 lacking JNK-dependent phosphorylation sites results in preserved tumor-suppressive function via pSmad3C in Ras-transformed cells while eliminating pSmad2/3L–mediated invasive capacity. Thus, specific inhibition of the JNK/pSmad2/3L pathway should suppress cancer progression by shifting Smad-dependent signaling from oncogenesis to tumor suppression. [Cancer Res 2007;67(11):5090–6]