tbuckley/cabot-search huggingface dataset:
Effects of the Herbal Extract PC-SPES on Microtubule Dynamics and Paclitaxel-Mediated Prostate Tumor Growth Inhibition
Authors: M. J. Bonham
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: PC-SPES is a botanical preparation shown to have efficacy in patients with androgen-dependent and androgen-independent prostate carcinoma. Several herbal constituents in PC-SPES inhibit tumor growth through cell cycle arrest and apoptosis, although the mechanisms of these activities are poorly defined. We sought to identify PC-SPES-induced changes in gene expression, specifically in those genes encoding cytoskeletal proteins that could be associated with PC-SPES-induced cytoxicity. Methods: LNCaP prostate carcinoma cells were treated with PC-SPES, and changes in gene expression were determined by complementary DNA (cDNA) microarray hybridization and northern blot analyses. PC-SPES and paclitaxel, a microtubule-stabilizing drug, effects on microtubules were assessed by immunofluorescence of treated cells and by in vitro tubulin polymerization assays. In vivo effects of PC-SPES and paclitaxel were assessed using CWR22R androgen-independent prostate cancer xenografts. All statistical tests were two-sided. Results: PC-SPES treatment of LNCaP cells for 24 hours altered the expression of 17 cytoskeletal genes. mRNA levels of α-tubulin decreased sevenfold. Although paclitaxel stabilized and PC-SPES treatment disrupted microtubule architecture in LNCaP cells, the combination of both agents had an intermediate effect. PC-SPES inhibited tubulin polymerization in vitro, even in the presence of paclitaxel. Compared with tumors in control mice (mean tumor volume = 2983 mm3, 95% confidence interval [CI] = 2380 to 3586 mm3), tumors were statistically significantly smaller in mice that received PC-SPES (mean tumor volume = 2018 mm3, 95% CI = 1450 to 2568 mm3; P = .028), paclitaxel (mean tumor volume = 1340 mm3, 95% CI = 697 to 1983 mm3; P<.001), or the combination of PC-SPES and paclitaxel (mean tumor volume = 1955 mm3, 95% CI = 1260 to 2650 mm3; P = .034). Conclusion: PC-SPES may interfere with microtubule polymerization. This activity has implications for the clinical management of patients with advanced prostate cancer who may be taking PC-SPES concurrently with microtubule-modulating chemotherapeutic agents, such as paclitaxel.
Dipyridamole-Induced Ischemia as a Prognostic Marker of Future Adverse Cardiac Events in Adult Patients With Hypertrophic Cardiomyopathy
Authors: Ettore Lazzeroni, Eugenio Picano, Letizia Morozzi, Anna Rita Maurizio, Giampaolo Palma, Roberta Ceriati, Emilio Iori, Angela Barilli, None (EPIC) Study Group, Subproject Hypertrophic Cardiomyopathy ;
Journal: Circulation (1997)

Background Myocardial ischemia may play a role in the natural history of hypertrophic cardiomyopathy (HCM). To assess the relative prevalence and the prognostic value of dipyridamole-induced ischemia, 79 patients with HCM and without concomitant coronary artery disease (53 men; mean age, 46±15 years) underwent a high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole test with 12-lead ECG and two-dimensional echo monitoring and were followed up for a mean of 6 years. Methods and Results Twenty-nine patients (37%) showed ECG (ie, ST depression ≥2 mV) signs of myocardial ischemia during dipyridamole test (group 1), whereas 50 (63%) had a negative test (group 2). No patient had transient wall motion abnormalities during the dipyridamole test. During the follow-up, 16 events (ie, left ventricular or atrial enlargement, unstable angina, syncope, atrial fibrillation, and bundle-branch block) occurred in 29 patients in group 1 and 5 in 50 patients in group 2 (55% versus 10%, P &lt;.001). Patients with a positive dipyridamole test showed worse 72-month event-free survival rates compared with patients with a negative test (36.2% versus 84.2%, P &lt;.001). A forward stepwise event-free survival analysis identified dipyridamole test positivity by ECG criteria (χ 2 =19.7, P =.0001), rest gradient (χ 2 =11.3, P =.0008), and age (χ 2 =4.1; P =.0413) as independent and additive predictors of subsequent events. Conclusions ECG signs of myocardial ischemia elicited by dipyridamole are frequent in patients with HCM and identify patients at higher risk of cardiac events, suggesting a potentially important pathogenetic role of inducible myocardial ischemia in determining adverse cardiac events in these patients.
Physician Attitudes Toward Foot Care Education and Foot Examination and Their Correlation With Patient Practice
Authors: Giorgia De Berardis, Fabio Pellegrini, Monica Franciosi, Maurizio Belfiglio, Barbara Di Nardo, Sheldon Greenfield, Sherrie H. Kaplan, Maria C.E. Rossi, Michele Sacco, Gianni Tognoni, Miriam Valentini, Antonio Nicolucci
Journal: Diabetes Care (2004)

Foot complications are one of the most serious causes of morbidity, disability, poor quality of life, and resource use among diabetic people (1). The adoption of preventive strategies to reduce the rate of foot problems thus represents an important priority. In fact, a strategy that includes prevention, patient and staff education, multidisciplinary treatment of foot complications, and close monitoring has been demonstrated to be very effective in reducing amputation rate (2).

In the context of a nationwide outcomes research program (the QuED project), we investigated several aspects related to foot care in 3,564 patients with type 2 diabetes enrolled by 125 diabetes outpatient clinics and …
Assembly of Productive T Cell Receptor δ Variable Region Genes Exhibits Allelic Inclusion
Authors: Barry P. Sleckman, Bernard Khor, Robert Monroe, Frederick W. Alt
Journal: The Journal of Experimental Medicine (1998)

The generation of a productive “in-frame” T cell receptor β (TCR β), immunoglobulin (Ig) heavy (H) or Ig light (L) chain variable region gene can result in the cessation of rearrangement of the alternate allele, a process referred to as allelic exclusion. This process ensures that most αβ T cells express a single TCR β chain and most B cells express single IgH and IgL chains. Assembly of TCR α and TCR γ chain variable region genes exhibit allelic inclusion and αβ and γδ T cells can express two TCR α or TCR γ chains, respectively. However, it was not known whether assembly of TCR δ variable regions genes is regulated in the context of allelic exclusion. To address this issue, we have analyzed TCR δ rearrangements in a panel of mouse splenic γδ T cell hybridomas. We find that, similar to TCR α and γ variable region genes, assembly of TCR δ variable region genes exhibits properties of allelic inclusion. These findings are discussed in the context of γδ T cell development and regulation of rearrangement of TCR δ genes.
Effect of Neomycin and Other Antibiotics on Serum Cholesterol Levels and on 7α-Dehydroxylation of Bile Acids by the Fecal Bacterial Flora in Man
Authors: PAUL SAMUEL, CHARLES M. HOLTZMAN, EDWARD MEILMAN, IGNACY SEKOWSKI
Journal: Circulation Research (1973)

Fresh feces from 25 patients were homogenized and incubated with labeled cholic or chenodeoxycholic acid. After 24 hours of incubation, the percent change to the 7α-dehydroxylated form was measured. In 11 patients, the oral administration of 2g of neomycin daily significantly reduced the levels of serum cholesterol (from an average of 316 mg/100 ml plasma to 237 mg/100 ml plasma) and markedly inhibited the extent of 7α-dehydroxylation of cholic acid (from 89% to 9%); in 2 patients whose serum cholesterol levels were not lowered, the degradation of cholic acid remained unchanged (control 93%, neomycin 91%). In 5 patients the administration of kanamycin reduced serum cholesterol levels (from 280 mg/100 ml plasma to 252 mg/100 ml plasma) and also inhibited 7α-dehydroxylation of cholic acid (from 92% to 21%); in 3 additional patients this drug failed to lower serum cholesterol concentrations and had no effect on bile acid degradation (control 91%, kanamycin 92%). Similar results were obtained with chloramphenicol in 3 patients, and equivocal results were obtained with chlortetracycline in 3 patients. The correlation coefficient between undegraded cholic acid and percent decrease in serum cholesterol concentrations ( r = 0.732) was statistically significant ( P &lt; 0.001). It is proposed that serum cholesterol levels might be controlled in part by the prevalence of bile acid-degrading bacteria within the gastrointestinal tract.
The effect of serum calcium levels on the rate of epidermal renewal in the rat
Authors: P.J. DYKES, R. MARKS
Journal: British Journal of Dermatology (1984)

The growth and differentiation of epidermal cells in vitro show a marked dependence on the calcium concentration of the medium. In this study the effect of experimentally produced hyper- and hypocalcaemia on the rat epidermis in vivo has been investigated. Hypercalcaemia, induced by injections of calcium chloride, produced a decrease in epidermal labelling index and some epidermal thinning. On the other hand hypocalcaemia, induced by calcitonin, failed to lead to changes in these measurements. The diurnal variation in epidermal labelling index and serum calcium levels was also measured. Whilst the labelling index decreased considerably over the period 09.00 hours to 18.00 hours, no significant changes were observed in serum calcium. These results suggest that while, under certain circumstances in vivo, the epidermal cell shows the same sensitivity to calcium as it does in vitro, calcium is not a major regulator of epidermopoiesis.
Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5–17 months in Kenya and Tanzania: a randomised controlled trial
Authors: Ally Olotu, John Lusingu, Amanda Leach, Marc Lievens, Johan Vekemans, Salum Msham, Trudie Lang, Jayne Gould, Marie-Claude Dubois, Erik Jongert, Preeti Vansadia, Terrell Carter, Patricia Njuguna, Ken O Awuondo, Anangisye Malabeja, Omar Abdul, Samwel Gesase, Neema Mturi, Chris J Drakeley, Barbara Savarese, Tonya Villafana, Didier Lapierre, W Ripley Ballou, Joe Cohen, Martha M Lemnge, Norbert Peshu, Kevin Marsh, Eleanor M Riley, Lorenz von Seidlein, Philip Bejon
Journal: The Lancet Infectious Diseases (2011)
Haematemesis and malaena as the first presentation of duodenal varices
Authors: L Ryan, R Bethune, K Habeeb
Journal: Journal of the Royal Society of Medicine (2010)

thickened area of mucosa enhanced vividly and contrast appeared in the lumen during the portal phase. The aetiology of this was uncertain from the CT scan, with possibly an inflammatory pathology being the cause, such as Crohn’s disease. The liver was normal and the portal veins were patent. At this point she was transferred to a regional specialist unit.
Benefits and Harms of Detecting Clinically Occult Breast Cancer
Authors: Eitan Amir, Philippe L. Bedard, Alberto Ocaña, Bostjan Seruga
Journal: JNCI Journal of the National Cancer Institute (2012)

Over the last few decades there has been an increase in the use of strategies to detect clinically occult breast cancer with the aim of achieving diagnosis at an earlier stage when prognosis may be improved. Such strategies include screening mammography in healthy women, diagnostic imaging and axillary staging in those diagnosed with breast cancer, and the use of follow-up imaging for the early detection of recurrent or metastatic disease. Some of these strategies are established, whereas for others there are inconsistent supportive data. Although the potential benefit of early detection of clinically occult breast cancer seems intuitive, use of such strategies can also be associated with harm. In this commentary, we provide an extended discussion on the potential benefits and harms of the routine and frequent use of screening interventions to detect clinically occult breast cancer and question whether we may be causing more harm than good.
Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53
Authors: Douglas Grossman, Paul J. Kim, Olivier P. Blanc-Brude, Douglas E. Brash, Simona Tognin, Pier Carlo Marchisio, Dario C. Altieri
Journal: Journal of Clinical Investigation (2001)

The inhibitor of apoptosis protein survivin has been implicated in both cell cycle control and apoptosis resistance. To discriminate between these different roles, we used transgenic expression of survivin in the skin as a model for cell proliferation, differentiation, and apoptosis. Transgenic mice expressing survivin under the control of a keratin-14 promoter developed normally, without histologic abnormalities of the skin or hair, epidermal hyperplasia, or developmental abnormalities of basal or suprabasal epidermis. Keratinocyte proliferation assessed under basal conditions, or after ultraviolet-B (UVB) irradiation, or phorbol ester stimulation was unchanged in survivin transgenic mice. In contrast, survivin expression inhibited UVB-induced apoptosis in vitro and in vivo (i.e., sunburn cell formation), whereas it did not affect Fas-induced cell death. When crossed with p53 knockout mice, transgenic expression of survivin in a p53+/– background substituted for the loss of a second p53 allele and further inhibited UVB-induced apoptosis. These data provide the first in vivo evidence that survivin inhibits apoptosis and suggest that this pathway may oppose the elimination of cancerous cells by p53.
Corneal Topography of Phase III Excimer Laser Photorefractive Keratectomy
Authors: Peter S. Hersh, Barbara H. Schwartz-Goldstein, Daniel Durrie, Timothy Cavanaugh, John Hunkeler, Marc Michelson, John Owen, Michael Gordon, Roger Steinert, Carmen Puliafito, Michael Raizman, Jay Pepose, Marc Michelson, John Owen, Michael Gordon, John R. Wright, R. Doyle Stulting, Keith Thompson, George O. Blaring, Stephen Brint, Roger Steinert, Carmen Puliafito, Michael Raizman, Daniel Durrie, Timothy Cavanaugh, John Hunkeler, Jay Pepose, J. Harley Galusha, Daniel H. Gold, Bernard A. Milstein
Journal: Ophthalmology (1995)
Mutational and Epigenetic Evidence for Independent Pathways for Lung Adenocarcinomas Arising in Smokers and Never Smokers
Authors: Shinichi Toyooka, Masaki Tokumo, Hisayuki Shigematsu, Keitaro Matsuo, Hiroaki Asano, Kunitoshi Tomii, Shuji Ichihara, Makoto Suzuki, Motoi Aoe, Hiroshi Date, Adi F. Gazdar, Nobuyoshi Shimizu
Journal: Cancer Research (2006)

Genetic and epigenetic alterations are considered to play important roles in lung cancer. Recent studies showed that EGFR and K-RAS mutations exhibited a mutually exclusive pattern in adenocarcinoma of the lung, suggesting the presence of two independent oncogenic pathways. However, it is unknown how epigenetic alterations were involved in lung carcinogenesis mediated by EGFR or K-RAS mutation. In this study, we examined the relationship between genetic and epigenetic alterations in 164 cases of lung adenocarcinoma. Somatic mutations were determined by direct sequence of EGFR exons 18 to 21 and K-RAS codons 12 and 13. Methylation status of p16(INK4a), RASSF1A, APC, RARbeta, and CDH13, frequently methylated in lung cancer, was determined by methylation-specific PCR and the degree of methylation was defined as the methylation index. Multivariate analysis adjusted for age, sex, and smoking dose showed that the probability of having EGFR mutation was significantly lower among those with p16(INK4a) and CDH13 methylation than in those without [p16(INK4a): odds ratio (OR), 0.07; 95% confidence interval (95% CI), 0.02-0.33; CDH13: OR, 0.34; 95% CI, 0.15-0.77] and the methylation index was significantly lower in EGFR mutant cases than in wild type (OR, 0.70; 95% CI, 0.52-0.95). By contrast, K-RAS mutation was significantly higher in p16(INK4a) methylated cases than in unmethylated cases (OR, 4.93; 95% CI, 1.54-15.7) and the methylation index was higher in K-RAS mutant cases than in wild type with marginal significance (OR, 1.46; 95% CI, 0.95-2.25). Our results indicate the differences in the evolvement of epigenetic alterations between the EGFR- and K-RAS-mediated tumorigenesis and suggest the specific interaction of genetic and epigenetic changes in tumorigenesis of lung cancer.
Aspirin Sensitizes Cancer Cells to TRAIL–Induced Apoptosis by Reducing Survivin Levels
Authors: Meiling Lu, Anne Strohecker, Feng Chen, Toni Kwan, Joshua Bosman, V. Craig Jordan, Vincent L. Cryns
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Although tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and agonistic antibodies targeting its receptors are promising cancer therapies because of their tumor selectivity, many tumors are resistant to TRAIL-based therapies. We examined whether the nonsteroidal anti-inflammatory drug aspirin sensitized cancer cells to TRAIL agonists in vitro and in vivo and investigated the underlying mechanism. Experimental Design: The effects of aspirin on sensitivity to TRAIL agonists and expression of apoptosis regulators was determined in human breast cancer cell lines and xenograft tumors. The specific role of survivin depletion in the TRAIL-sensitizing effects of aspirin was determined by silencing survivin. Results: Aspirin sensitized human breast cancer cells, but not untransformed human mammary epithelial cells, to TRAIL-induced caspase activation and apoptosis by a cyclooxygenase-2–independent mechanism. Aspirin also sensitized breast cancer cells to apoptosis induced by a human agonistic TRAIL receptor-2 monoclonal antibody (lexatumumab). Aspirin treatment led to G1 cell cycle arrest and a robust reduction in the levels of the antiapoptotic protein survivin by inducing its proteasomal degradation, but did not affect the levels of many other apoptosis regulators. Silencing survivin with small interfering RNAs sensitized breast cancer cells to TRAIL-induced apoptosis, underscoring the functional role of survivin depletion in the TRAIL-sensitizing actions of aspirin. Moreover, aspirin acted synergistically with TRAIL to promote apoptosis and reduce tumor burden in an orthotopic breast cancer xenograft model. Conclusions: Aspirin sensitizes transformed breast epithelial cells to TRAIL-based therapies in vitro and in vivo by a novel mechanism involving survivin depletion. These findings provide the first in vivo evidence for the therapeutic utility of this combination.
Clinical Characteristics, 4-Year Course, and DSM-IV Classification of Patients With Nonaffective Acute Remitting Psychosis
Authors: Ramin Mojtabai, Ezra S. Susser, Evelyn J. Bromet
Journal: American Journal of Psychiatry (2003)

The authors examined the clinical characteristics and 48-month illness course of cases of nonaffective acute remitting psychosis and described the classification of these cases in the DSM-IV system.The data were derived from the Suffolk County (N.Y.) Mental Health Project, a study of first-admission patients with psychotic disorders admitted to psychiatric facilities between September 1989 and December 1995. The authors compared the demographic and clinical characteristics, 48-month course, and longitudinal research diagnoses of 16 patients with nonaffective acute remitting psychosis, defined by onset in 2 weeks or less and duration of less than 6 months, to those of 26 patients with other nonaffective remitting psychoses.Nonaffective acute remitting psychosis had a distinctly benign course-46% of the patients remained in full remission throughout the 48-month follow-up, compared with 14% of patients with other remitting psychoses. Nonaffective acute remitting psychosis was also associated with fewer negative symptoms than other remitting psychoses. By 24-month follow-up, only 6% of the patients with nonaffective acute remitting psychosis, compared with 77% of the patients with other remitting psychoses, received a research diagnosis of schizophrenia or schizoaffective disorder, whereas 44% of patients with nonaffective acute remitting psychosis, compared with 12% of patients with other remitting psychoses, were given the residual diagnosis of psychotic disorder not otherwise specified.Nonaffective acute remitting psychosis is a highly distinctive yet not adequately classified condition. Better delineation of nonaffective acute remitting psychosis in current diagnostic systems could lead to better understanding of this condition and improve the applicability of diagnostic systems in developing countries, where these conditions are more common than in industrialized countries.
Studies of the Metabolic Activity of Leukocytes from Patients with a Genetic Abnormality of Phagocytic Function*
Authors: Beulah Holmes, Arthur R. Page, Robert A. Good
Journal: Journal of Clinical Investigation (1967)

Polymorphonuclear leukocytes from patients with chronic granulomatous disease respond to the phagocytosis of latex particles with normal increments in glucose consumption, lactate production, Krebs' cycle activity, and lipid turnover. The leukocytes of these patients fail to show normal increments in respiration, direct oxidation of glucose, and hydrogen peroxide formation during particle uptake. It appears that the stimulation of respiration with the formation of hydrogen peroxide and stimulation of the direct oxidative pathway of glucose metabolism are closely linked to degranulation and intracellular killing of bacteria by polymorphonuclear leukocytes.
Paf-acether synthesis by Helicobacter pylori.
Authors: Y Denizot, I Sobhani, J C Rambaud, M Lewin, Y Thomas, J Benveniste
Journal: Gut (1990)

Clinical studies suggest that Helicobacter pylori may play a role in the pathogenesis of gastroduodenal ulcers in man but direct evidence of mucosal injury by this microorganism is still lacking. Paf-acether (paf) causes a number of disorders including ischaemic bowel necrosis and gastroduodenal ulceration. Since paf is produced by Escherichia coli, we investigated whether it could be synthesised by H pylori. Five H pylori isolates were collected from antral biopsy specimens from patients with gastritis and duodenal ulcer and cultured with selective antibiotics. Colonies obtained from both blood agar and brucella broth medium were used. Paf was determined by platelet aggregation assay after ethanolic extraction and subsequent purification by high performance liquid chromatography. Paf was detected in H pylori in blood agar plates (680 (390) pg paf/1 x 10(6) organisms) but not in bacteria cultured on brucella broth medium. Supplementation of the latter medium with lyso paf and acetyl-CoA, two paf precursors present in high amounts in the mammalian intestine, induced paf production in three of five isolates. The platelet aggregating material extracted from H pylori exhibited biological and physiochemical characteristics identical to those of paf released from eukaryotic cells. These findings suggest that H pylori may add to the local production of paf in inflamed gastric mucosa.
Management of sepsis in neutropenic patients: guidelines from the infectious diseases working party of the German Society of Hematology and Oncology
Authors: O. Penack, D. Buchheidt, M. Christopeit, M. von Lilienfeld-Toal, G. Massenkeil, M. Hentrich, H. Salwender, H.-H. Wolf, H. Ostermann
Journal: Annals of Oncology (2010)