tbuckley/cabot-search huggingface dataset:
Abstract 3321: The benefits from combined temozolomide and sunitinib in medulloblastoma cells: The antitumor effect, inhibition of invasiveness, and blocking of cancer stem cells
Authors: Dong-Ok Kim, Young Shin Ra
Journal: Cancer Research (2011)

Abstract Objectives: Medulloblastoma is the most common malignant and metastatic pediatric brain tumor in children. Angiogenesis inhibitors, such as sunitinib, represent a promising strategy to improve glioblastoma (GBM) tumor response. Temozolomide (TMZ) also became the standard of care for GBM patients by removing alkyl groups from the O6-position of guanine. But, there is little evidence about migration and invasion study on medulloblastoma cells treated with sunitinib or TMZ. In this study, we identified the effects of sunitinib or TMZ only, and the combination of them on migration and invasiveness in medulloblastoma cell line (DAOY). Also the characteristics of cancer stem cells were investigated. Methods and Results: The cell proliferation rate showed TMZ (1000µM) 70%, sunitinib (62.5µM) 60%, and the combination of TMZ and sunitinib (1000/62.5µM) 35% at 72hr after treatment with the drugs in DAOY cells. Treatment with sunitinib in addition to TMZ in the cells demonstrated more G2/M arrest than cells treated respective drugs at 24hr exposure of the drugs from cell cycle analysis. Through Rhodamine phalloidin staining, we also observed change of cell size and F-actin alterations in all cells treated TMZ, sunitinib only or the combination of the reagents, in contrast to cells treated DMSO as a control. And, in invasion assay using Matrigel chamber, the cells treated with combination of drugs were inhibited invasiveness the most when compared with control, sunitinib, and TMZ only at 72hr after exposure to the drugs. Moreover, when the cells were treated with sunitinib and TMZ simultaneously, migration ability from wound-healing assay represented higher than in cells treated TMZ or sunitinib only during exposure of 24hr. We investigated properties of cancer stem cells as well as characteristics of migration and invasion in cells treated the drugs analyzing the expression of protein during exposure of 24, 48, 72hr by western blotting. As a result, we identified the decreased levels of the protein such as p-PDGFR-β, p-VEGFR1, integrin-β1, MMP-9, CD44, Rac1 as migration and invasion markers, nestin, CD133, Oct3/4, Sox2 as cancer stem cell markers and O6-methylguanine methyltransferase(MGMT). Conclusions: Taken together, the combination therapy functions as very effective therapeutic tool in terms of, not only inhibititor of proliferation, migration and invasiveness, but also cancer stem cells in medulloblastoma cell line. 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 3321. doi:10.1158/1538-7445.AM2011-3321
Impaired 24,25-Dihydroxyvitamin D Production in Anephric Human and Pig
Authors: Ronald L. Horst, E. Travis Littledike, Richard W. Gray, Joseph L. Napoli
Journal: Journal of Clinical Investigation (1981)

Plasma 25-hydroxyvitamin D and 24, 25-dihydroxy-vitamin D [24,25-(OH)2D] concentrations were measured in normal and chronically dialyzed anephric humans and pigs. Measurement of the 24, 25-(OH)2D was preceded by three purification steps involving one Sephadex LH-20 column and two high-pressure liquid chromatographic columns. The final high-pressure liquid chromatography step involved resolution of 25-hydroxy-vitamin D3-26,23 lactone and 25,26-dihydroxy-vitamin D2 from 24,25-dihydroxyvitamin D2 and 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3]. The total 25-hydroxyvitamin D [25-hydroxyvitamin D2 plus 25-hydroxyvitamin D3 (25-OHD3)] was 31.7±3.6 ng/ml in the plasma of eight anephric human subjects and 40.1±3.7 ng/ml in five normal human subjects. Six of the eight anephric patients had undetectable (<0.2 ng/ml) 24,25-(OH)2D concentrations. Two of the eight patients had very low (0.51 and 0.41 ng/ml), but detectable, 24,25-dihydroxyvitamin D2. The normal human volunteers had plasma 24,25-(OH)2D concentrations of 2.8±0.7 ng/ml. Chronically dialyzed anephric and normal pigs were given intramuscular injections of massive amounts (5 × 106 IU) of vitamin D3 immediately after surgery (day 0) and again on day 7. In anephric pigs, plasma 25-OHD3 progressively rose from 12±4 ng/ml on day 0 to 705±62 ng/ml on day 10. The 25-OHD3 concentrations in normal pigs rose from 8±2 ng/ml on day 0 to 439±64 ng/ml on day 10. Plasma 25-OHD3 was higher in anephrics throughout the experiment, and concentrations were significantly higher (P < 0.05) on days 9 and 10. Plasma 24,25-(OH)2D3 concentrations declined progressively in anephric pigs from 3.6±0.6 ng/ml on day 0 to 3.2±0.7 ng/ml on day 2. During days 4-10, plasma 24,25-(OH)2D3 was not apparent until plasma 25-OHD3 was >400 ng/ml. In control pigs, plasma 24,25-(OH)2D3 was elevated from 4.3±0.6 ng/ml on day 0 to 178±2.7 ng/ml on day 3. Plasma 24,25-(OH)2D3 was significantly higher (P < 0.05) in controls on days 1-8. At the end of the experiment (day 10), 24,25-(OH)2D3 concentrations were similar and not significantly different in both groups (87.0±18.4 ng/ml in anephric and 110.3±32.1 ng/ml in normal pigs). The identity of the 24,25-(OH)2D3 isolated from anephric pig plasma was confirmed by mass spectroscopy. Our data suggest that anephric humans receiving normal dietary levels of vitamin D3 have little or no ability to produce 24,25-(OH)2D. However, we have shown that pigs produce 24,25-(OH)2D3 when plasma 25-OHD3 is extremely high (>400 ng/ml).
Marked antiinflammatory effects of decentralization of the superior cervical ganglia.
Authors: K Ramaswamy, R Mathison, L Carter, D Kirk, F Green, J S Davison, D Befus
Journal: The Journal of Experimental Medicine (1990)

Intravenous challenge with parasite antigens in Nippostrongylus brasiliensis-sensitized rats resulted in anaphylactic shock and, in some animals, death. Surviving animals showed significant drop in mean arterial blood pressure, cardiac output, and blood flow to the trachea, bronchioles, and mesentery. After anaphylaxis, changes in the cellular and protein composition in bronchoalveolar lavage fluids (BALF) were assessed. 8 h after antigen challenge, there was significant influx of inflammatory cells and an increase in the levels of histamine and serum-derived immunoglobulins (IgG and IgM) in BALF. Chemotactic activity for neutrophils was also present in BALF. Once we established this anaphylaxis-induced model of pulmonary inflammation, we sought to determine whether or not the superior cervical ganglia (SCG) modulate this inflammation. We performed bilateral superior cervical ganglionectomy or decentralization of the SCG. Our results show that decentralization significantly reduced mortality (by 68%) after anaphylaxis. Furthermore, the increases in levels of serum-derived proteins, histamine, and influx of cells (especially neutrophils) observed in BALF after anaphylaxis were attenuated by both decentralization and ganglionectomy. By contrast, hemodynamic parameters in the respiratory tract and the presence of neutrophil chemotactic activity in BALF were not influenced by decentralization. Thus, the severity of pulmonary inflammation initiated by systemic anaphylaxis is depressed by bilateral ganglionectomy or decentralization of SCG.
Promoter-targeted siRNAs Induce Gene Silencing of Simian Immunodeficiency Virus (SIV) Infection In Vitro
Authors: Heidi GW Lim, Kazuo Suzuki, David A Cooper, Anthony D Kelleher
Journal: Molecular Therapy (2008)

RNA interference is a conserved process by which sequence-specific double-stranded RNA is converted into small interfering double-stranded RNAs (siRNAs) that can induce gene silencing via two pathways: post-transcriptional gene silencing and transcriptional gene silencing (TGS). We previously reported TGS of human immunodeficiency virus-1 (HIV-1) could be induced by siRNAs targeting regions within its 5'-long-terminal repeat (5'LTR) promoter region. Here we show that promoter-targeted siRNAs can also induce silencing of simian immunodeficiency virus (SIV) replication by similar mechanisms. Suppression of productive infection was achieved in two different cell lines: a CD4, CCR5, CXCR4 expressing HeLa cell line (MAGIC-5) and in a human lymphoid cell line (CEMx174). HpaII digestion demonstrated induction of methylation at a CpG site within the SIV promoter region following siRNA-induced suppression. Both 5-azacytidine (5-AzaC) and trichostatin A (TSA), inhibitors of DNA methyltransferases (DNMTs) and histone deacetylation, respectively, partially reversed the silencing effect. Furthermore, using chromatin immunoprecipitation (ChIP) assays we found enrichment in the region of the LTR of heterochromatin markers dimethylated histone 3 lysine 9 (H3K9) and trimethylated histone 3 lysine 27 (H3K27) in the siRNA silenced cultures. Together, these results strongly suggest certain siRNAs targeting the promoter region of SIV can effect viral silencing through the induction of epigenetic changes.
Pulmonary Function and Exercise-associated Changes with Chronic Low-Level Paraquat Exposure
Authors: Marc B. Schenker, Maria Stoecklin, Kiyoung Lee, Rafael Lupercio, R. Jorge Zeballos, Paul Enright, Tamara Hennessy, Laurel A. Beckett
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The present study was undertaken to test the hypothesis that chronic, low-level paraquat exposure causes restrictive lung function with gas transfer impairment. Three hundred thirty-eight Costa Rican farm workers from banana, coffee, and palm oil farms completed a questionnaire, spirometry, and a test of single-breath carbon monoxide diffusing capacity. Subjects 40 years of age or older, without other medical risk factors, completed maximal cardiopulmonary exercise tests. Most (66.6%) were paraquat handlers; 24.8% of handlers and 27.3% of nonhandlers reported current cigarette smoking. In linear regression models, cumulative paraquat exposure was not an independent predictor of VA, carbon monoxide diffusing capacity, peak oxygen uptake, FVC, or oxygen pulse peak. However, the ventilatory equivalent for CO2, although within normal range, was significantly higher with increased cumulative paraquat exposure. Oxygen desaturation greater than 5% from rest to peak exercise had an odds ratio of 1.7 (95% confidence interval = 0.9–3.0) with the cumulative paraquat exposure index in models adjusted for age, weight, and smoking status. The association of paraquat exposure with ventilatory equivalent and oxygen desaturation suggests that paraquat may be associated with subclinical gas exchange abnormalities, but overall these findings are consistent with no clinically significant increases in interstitial thickening or restrictive lung disease among this population.
Spinal Cerebrospinal Fluid Leak Demonstrated by Retrograde Myeloscintigraphy
Authors: EUGENE D. SILVERMAN, WILLIAM B. DAVIS, JOHN C. HARBERT, STANLEY M. LEVENSON
Journal: Clinical Nuclear Medicine (1981)

Cerebrospinal fluid (CSF) leaks may occur following spinal surgery and are commonly associated with infection. These leaks can be successfully evaluated with retrograde myeloscintigraphy using the same techniques applied in diagnosing CSF otorrhea and rhinorrhea. This report describes the utility of this procedure in differentiating a process due solely to postoperative infection from one that involves both an inflammatory site and a fistulous tract with the subarachnoid space.
Gastric ulcer healing with tripotassium dicitrato bismuthate and subsequent relapse.
Authors: D R Sutton
Journal: Gut (1982)

Fifty patients with endoscopically proven gastric ulcers completed a one month double-blind randomised trial of tripotassium dicitrato bismuthate (TBD) (DeNol) compared with an identical placebo. Ulcer healing occurred in 18 (72%) of the 25 patients given TDB and in nine (36%) of the patients given placebo. The TDB group experienced significantly less pain than the placebo group. During a follow-up of 29 patients with healed ulcers for up to 44 months, relapse occurred in 13 (45%). It was highest in the first three months (27%) and had risen to 41% at two years.
Similar transplantation outcomes in patients bridged with cardiac assist devices for acute cardiogenic shock versus chronic heart failure
Authors: Stavros G. Drakos, Abdallah G. Kfoury, James W. Long, James C. Stringham, Edward M. Gilbert, Benjamin D. Horne, Mary‐Beth E. Hagan, Karah Nelson, Dale G. Renlund
Journal: European Journal of Heart Failure (2007)
THE RELATIVE IMPORTANCE OF VALVULAR AND MUSCULAR LESIONS IN DISEASES OF THE HEART.
Authors: SOLOMON SOLIS-COHEN
Journal: JAMA (1901)

It would be incorrect to say that the importance of affections of the myocardium has been but recently recognized; yet it is probably true that the attention of teachers and authors has been much more actively given to these affections during the last four or five years, and that among physicians not engaged in teaching or writing, the subject, while not ignored, has not even yet received the attention it deserves. One reason for this is that until recently, at least, in the didactic lectures, in the clinical lectures, in the ward classes, and in the quiz room, so much stress has been laid on the diagnosis of valvular lesions and the recognition of cardiac murmurs that the average student leaves college with the conception of valvular murmurs and heart disease as synonymous. In post-graduate teaching I have frequently had experienced men, as well as recent graduates, report that a
Intracerebral Crises During Treatment of Diabetic Ketoacidosis
Authors: Arlan L Rosenbloom
Journal: Diabetes Care (1990)

Sixty-nine instances of intracerebral complications of diabetic ketoacidosis (DKA), including 29 unpublished occurrences, were analyzed to determine predictive factors, the frequency of other disorders resembling cerebral edema, the effectiveness of intervention to reduce intracranial pressure, and whether any etiologic considerations appeared valid. The review failed to implicate rate of hydration, tonicity of administered fluids, rate of correction of glycemia, or use of bicarbonate. Infants and young children (&amp;lt;5 yr of age) were disproportionately represented (33%), as were new-onset patients (62%). Approximately 20% of patients were found to have localized basilar edema, hemorrhage, thromboses, or infection by computed tomography scan or on postmortem examination. The histories of 50% of the patients suggested a period of dramatic neurological change preceding respiratory arrest (RA) during which intervention might be effective. Twenty-three patients were treated for increased intracranial pressure before RA; 13 patients survived in an independent functional state, and 3 survived in a severely disabled or vegetative state. Only 3 of the remaining 46 patients survived normally: 2 were untreated and never developed RA, and 1 was given mannitol at the onset of apnea. This review supports close neurological monitoring and intervention to reduce intracranial pressure when there are definite signs of neurological compromise. However, treatment appears to be successful in only 50% of patients who give sufficient warning for such intervention, and they comprised half of the study population. Therefore, prevention of DKA remains the most important goal to avoid intracerebral complications.
Effect of injection and sampling site on dye dilution curves during hypotension
Authors: J. P. BLACKBURN, J. M. LEIGH
Journal: Cardiovascular Research (1972)

Cardiac output was estimated by right-sided, left-sided, and transpulmonary dye curves in dogs. The time for blood recirculated through the coronary circulation to reach the densitometer was measured. The effects of various hypotensive agents were investigated. Coronary recirculation caused errors in the dye curves only in profound haemorrhagic shock, as halothane produced large increases in coronary circulation time. Systematic differences between transpulmonary and right or left sided dye curves were found.
Surgeons' ties to device manufacturers under investigation
Authors: Ray Moynihan
Journal: BMJ (2005)

The US Justice Department is investigating the financial ties between orthopaedic surgeons and companies that sell medical devices. Some leading surgical device manufacturers last week said that they had received subpoenas from the department requesting extensive details about their payments to surgeons.

According to the companies that received them, the subpoenas asked for any and all consulting contracts, professional service agreements, or remuneration agreements with surgeons, trainee surgeons, or medical school graduates who use hip or knee …
Diabetes and Impaired Glucose Tolerance in Three American Indian Populations Aged 45-74 Years: The Strong Heart Study
Authors: Elisa T Lee, Barbara V Howard, Peter J Savage, Linda D Cowan, Richard R Fabsitz, Arvo J Oopik, Jeunliang Yeh, Oscar Go, David C Robbins, Thomas K Welty
Journal: Diabetes Care (1995)

OBJECTIVE To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors: age, obesity, family history of diabetes, and amount of Indian ancestry. RESEARCH DESIGN AND METHODS This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio. RESULTS A total of 4,549 eligible participants were examined, and diabetes status was determined for4,304(1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status. CONCLUSIONS Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs shoula be expanded to include those with IGT to improve glycemie control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.
A piece of my mind. Flaky
Authors: R. A. Katz
Journal: JAMA (1989)

It was a beautiful, warm afternoon in September when I first met Daniel. He stood rather apprehensively in the center of the examination room, dressed, it seemed, for winter. On a day when I had already seen several other students dressed in T-shirts and shorts, Daniel wore a long-sleeved flannel shirt buttoned to the neck and baggy corduroy slacks. His large, sad eyes were almost hidden by his hair, which was carefully combed down over his forehead, giving him the appearance of someone who might have been just released after being institutionalized for many years. In fact, he was a new college freshman in the school of engineering at the state university near my office, and had been referred to me by the student health service. "Doc," he blurted, "I can't stand it anymore. I just want to be able to be with other people without having them look at me like I'm a leper, like they might catch what I have. I want to be able to hold a girl's hand, to go to the beach in the summer. Please. Please help me." As he began to undress, fine silvery scales fell freely in a shower around him. I was reminded of the forlorn snowman in a fluid-filled paperweight that would
Beneficial effects of conversion from cyclosporin to azathioprine after kidney transplantation
Authors: A.A.M.J. Hollander, J.L.C.M. van Saase, L.A. van Es, F.J. van derWoude, H.J. van Bockel, J.L.C.M. van Saase, A.M.M. Kootte, W.T. van Dorp
Journal: The Lancet (1995)
Effect of bepridil in patients with chronic stable angina: results of a multicenter trial.
Authors: J A Hill, J T O'Brien, J S Alpert, J M Gore, R M Zusman, D Christensen, C A Boucher, G Vetrovec, J S Borer, C Friedman
Journal: Circulation (1985)

The effects of bepridil, a calcium antagonist with a half-life of approximately 42 hr, were assessed in a double-blind, randomized, placebo-controlled crossover trial. Forty-four patients (39 men, five women) with exercise-induced angina pectoris and ST segment depression with exercise testing (modified Bruce protocol) were studied. Compared with placebo bepridil (400 mg daily) increased total exercise time, time to onset of angina, time to 1 mm of ST segment depression, time to 2 mm of ST segment depression, and total work achieved (all p less than or equal to .001). Both frequency of angina and nitroglycerin consumption decreased during the bepridil compared with the placebo period (p = .02 and .03, respectively). Minor side effects were noted during both the bepridil and placebo phases. Four patients experienced side effects that limited therapy (dizziness in three and abnormal results of liver function tests in one) and one patient died during the bepridil phase. This study suggests that bepridil, 400 mg daily, is effective for the treatment of exercise-induced myocardial ischemia and angina pectoris.
Dapsone and renal papillary necrosis.
Authors: B I Hoffbrand
Journal: BMJ (1978)

sistently ingested eight tablets (80 mg) daily without any side effects.Because he could not get metoclopramide without prescription while his regular doctor was away, he abruptly stopped taking the drug.Ten days later he progressively developed severe persistent facial dyskinesia consisting of repetitive involuntary movements of the lips, jaws, cheeks, and tongue.The latter were mainly constant, forceful sucking, chewing, grimacing, and rapid protrusions of the tongue.Results of general physical and neurological examinations were otherwise normal.Blood count, sedimentation rate, and biochemical and serological examinations showed nothing abnormal.The patient had never received other drugs known -to be associated with involuntary movements, such as phenothiazines or butyrophenones.Readministration of metoclopramide at a daily dose of 30 mg resulted in almost complete disappearance of the involuntary movements.Another attempt to withdraw the drug was associated with-recurrence of the dyskinesia, which subsided when metoclopramide was given again.