tbuckley/cabot-search huggingface dataset:
Quantification of microheterogeneity in glioblastoma multiforme with ex vivo high-resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy
Authors: L L Cheng, D C Anthony, A R Comite, P M Black, A A Tzika, R G Gonzalez
Journal: Neuro-Oncology (2000)

Microheterogeneity is a routinely observed neuropathologic characteristic in brain tumor pathology. Although microheterogeneity is readily documented by routine histologic techniques, these techniques only measure tumor status at the time of biopsy or surgery and do not indicate likely tumor progression. A biochemical screening technique calibrated against pathologic standards would greatly assist in predicting tumor progression from its biological activity. Here we demonstrate for the first time that proton magnetic resonance spectroscopy (1H MRS) with high-resolution magic-angle spinning (HRMAS), a technique introduced in 1997, can preserve tissue histopathologic features while producing well-resolved spectra of cellular metabolites in the identical intact tissue specimens. Observed biochemical alterations and tumor histopathologic characteristics can thus be correlated for the same surgical specimen, obviating the problems caused by tumor microheterogeneity. We analyzed multiple specimens of a single human glioblastoma multiforme surgically removed from a 44-year-old patient. Each specimen was first measured with HRMAS 1H MRS to determine tumor metabolites, then evaluated by quantitative histopathology. The concentrations of lactate and mobile lipids measured with HRMAS linearly reflected the percentage of tumor necrosis. Moreover, metabolic ratios of phosphorylcholine to choline correlated linearly with the percentage of the highly cellular malignant glioma. The quantification of tumor metabolic changes with HRMAS 1H MRS, in conjunction with subsequent histopathology of the same tumor specimen, has the potential to further our knowledge of the biochemistry of tumor heterogeneity during development, and thus ultimately to improve our accuracy in diagnosing, characterizing, and evaluating tumor progression.
Irinotecan or oxaliplatin combined with leucovorin and 5-fluorouracil as first-line treatment in advanced colorectal cancer: a multicenter, randomized, phase II study
Authors: H.P. Kalofonos, G. Aravantinos, P. Kosmidis, P. Papakostas, T. Economopoulos, M. Dimopoulos, D. Skarlos, A. Bamias, D. Pectasides, S. Chalkidou, M. Karina, A. Koutras, E. Samantas, C. Bacoyiannis, G.F. Samelis, G. Basdanis, F. Kalfarentzos, G. Fountzilas
Journal: Annals of Oncology (2005)
Novel origins of copy number variation in the dog genome
Authors: Jonas Berglund, Elisa M Nevalainen, Anna-Maja Molin, Michele Perloski, Catherine André, Michael C Zody, Ted Sharpe, Christophe Hitte, Kerstin Lindblad-Toh, Hannes Lohi, Matthew T Webster
Journal: Genome biology (2012)

Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution.
Growth Factors, Nutrient Signaling, and Cardiovascular Aging
Authors: Luigi Fontana, Manlio Vinciguerra, Valter D. Longo
Journal: Circulation Research (2012)

Growth factors regulated by specific macronutrients have been shown to promote aging and accelerate mortality in the majority of the organisms studied. In particular, the enzymes activated by growth hormone, insulin, and insulin-like growth factor-1 in mammals and their orthologs in simple model organisms represent perhaps the best-understood proteins involved in the aging process. Dietary restriction, which reduces the level of insulin-like growth factor-1 and of other growth factors, has been associated with protection from diabetes, cancer, and cardiovascular diseases, and deficiencies in growth hormone signaling and insulin-like growth factor-1 are strongly associated with protection from cancer and diabetes in both mice and humans; however, their role in cardiac function and cardiovascular diseases is controversial. Here, we review the link between growth factors, cardiac function, and heart disease with focus on the cardioprotective and sensitizing effect of growth factors in both model organisms and humans.
Multicenter phase II study of gemcitabine and oxaliplatin in advanced nasopharyngeal carcinoma—correlation with excision repair cross-complementing-1 polymorphisms
Authors: B.B.Y. Ma, E.P. Hui, S.C.C. Wong, S.Y. Tung, K.K. Yuen, A. King, S.L. Chan, S.F. Leung, M.K. Kam, B.K.H. Yu, B. Zee, A.T.C. Chan
Journal: Annals of Oncology (2009)
Air Pollution from Road Traffic and Systemic Inflammation in Adults: A Cross-Sectional Analysis in the European ESCAPE Project
Authors: Timo Lanki, Regina Hampel, Pekka Tiittanen, Silke Andrich, Rob Beelen, Bert Brunekreef, Julia Dratva, Ulf De Faire, Kateryna B. Fuks, Barbara Hoffmann, Medea Imboden, Pekka Jousilahti, Wolfgang Koenig, Amir A. Mahabadi, Nino Künzli, Nancy L. Pedersen, Johanna Penell, Göran Pershagen, Nicole M. Probst-Hensch, Emmanuel Schaffner, Christian Schindler, Dorothea Sugiri, Wim J.R. Swart, Ming-Yi Tsai, Anu W. Turunen, Gudrun Weinmayr, Kathrin Wolf, Tarja Yli-Tuomi, Annette Peters
Journal: Environmental Health Perspectives (2015)

BackgroundExposure to particulate matter air pollution (PM) has been associated with cardiovascular diseases.ObjectivesIn this study we evaluated whether annual exposure to ambient air pollution is associated with systemic inflammation, which is hypothesized to be an intermediate step to cardiovascular disease.MethodsSix cohorts of adults from Central and Northern Europe were used in this cross-sectional study as part of the larger ESCAPE project (European Study of Cohorts for Air Pollution Effects). Data on levels of blood markers for systemic inflammation—high-sensitivity C-reactive protein (CRP) and fibrinogen—were available for 22,561 and 17,428 persons, respectively. Land use regression models were used to estimate cohort participants’ long-term exposure to various size fractions of PM, soot, and nitrogen oxides (NOx). In addition, traffic intensity on the closest street and traffic load within 100 m from home were used as indicators of traffic air pollution exposure.ResultsParticulate air pollution was not associated with systemic inflammation. However, cohort participants living on a busy (&gt; 10,000 vehicles/day) road had elevated CRP values (10.2%; 95% CI: 2.4, 18.8%, compared with persons living on a quiet residential street with &lt; 1,000 vehicles/day). Annual NOx concentration was also positively associated with levels of CRP (3.2%; 95% CI: 0.3, 6.1 per 20 μg/m3), but the effect estimate was more sensitive to model adjustments. For fibrinogen, no consistent associations were observed.ConclusionsLiving close to busy traffic was associated with increased CRP concentrations, a known risk factor for cardiovascular diseases. However, it remains unclear which specific air pollutants are responsible for the association.CitationLanki T, Hampel R, Tiittanen P, Andrich S, Beelen R, Brunekreef B, Dratva J, De Faire U, Fuks KB, Hoffmann B, Imboden M, Jousilahti P, Koenig W, Mahabadi AA, Künzli N, Pedersen NL, Penell J, Pershagen G, Probst-Hensch NM, Schaffner E, Schindler C, Sugiri D, Swart WJ, Tsai MY, Turunen AW, Weinmayr G, Wolf K, Yli-Tuomi T, Peters A. 2015. Air pollution from road traffic and systemic inflammation in adults: a cross-sectional analysis in the European ESCAPE project. Environ Health Perspect 123:785–791; http://dx.doi.org/10.1289/ehp.1408224
Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold.
Authors: D Prié, F B Blanchet, M Essig, J P Jourdain, G Friedlander
Journal: Journal of the American Society of Nephrology (1998)

It has been shown that an acute infusion of dipyridamole increased renal phosphate reabsorption in rats and humans. A prospective study was performed to determine whether chronic treatment by dipyridamole given orally could decrease renal phosphate leak and increase serum phosphorus in patients with idiopathic low renal phosphate threshold (TmPO4/GFR < 0.77 mM). Sixty-four patients with low TmPO4/GFR were included and treated with dipyridamole (75 mg, 4 times daily) for more than 12 mo. Serum phosphorus, TmPO4/GFR, parathyroid hormone, serum calcium, and 1,25-dihydroxyvitamin D were measured sequentially before treatment, and after 3, 6 to 9, and 12 mo of treatment. Under chronic treatment with dipyridamole, TmPO4/GFR and serum phosphorus significantly increased in 80% of patients within 3 mo, with maximal values reached within 9 mo. This improvement persisted after 12 mo of treatment. In 28 patients, 1,25-dihydroxyvitamin D concentrations were above the normal range (> 42 pg/ml) and normalized in parallel with the increase of serum phosphorus. The 24-h calcium excretion (which was initially increased in patients with high vitamin D concentrations) and urolithiasis decreased under treatment. Ionized serum calcium and parathyroid hormone remained unchanged. After 2 yr, treatment was discontinued in three patients; serum phosphorus and TmPO4/GFR decreased within 1 mo after discontinuation. Dipyridamole at a dose of 75 mg 4 times daily increases low TmPO4/GFR and improves hypophosphatemia in patients with renal phosphate losses and can be used to treat these patients.
Watchful Waiting, Temporarily Deferred Therapy, or Active Surveillance?
Authors: Chris Parker
Journal: Journal of Clinical Oncology (2005)

I was interested to read the report of Carter et al of a conservative management strategy for early prostate cancer, 1 and I agree with the authors that the term "watchful waiting" does not accurately describe their strategy.Given the overdiagnosis and lead-time bias associated with prostate-specific antigen (PSA) screening, 2 the natural history of prostate cancer following diagnosis is now far more favorable than it was in the pre-PSA era, making a conservative management strategy an attractive option for many patients.However, clinicians and patients need to understand the important distinctions between the different conservative strategies now available.The term watchful waiting was widely used during the pre-PSA era to describe a policy of observation with palliative treatment for symptomatic cancer progression.Such a policy remains appropriate for patients who, by virtue of age and comorbidities, have a relatively short life expectancy and do not have a radical treatment option.A second, and quite distinct, approach to favorable-risk early prostate cancer is to determine the need for radical treatment based on biochemical or histologic evidence of disease progression during close monitoring.The aim of this approach is to target curative treatment to the minority of patients who need it, so that the majority are spared the side effects of unnecessary treatment.This strategy was first described by Richard Choo et al as, "watchful observation with selective delayed intervention." 3At the Royal Marsden Hospital, we use the term "active surveillance" to describe this strategy. 4 These initial studies have demonstrated the feasibility of this approach, which offers patients a realistic hope of avoiding treatment side effects without detriment to their survival.Active surveillance requires a clear definition of the indications for radical treatment (usually based on PSA doubling time and the results of repeat biopsies), together with a commitment to the policy from both patient and clinician.If these are lacking, the result will be "temporarily deferred therapy," as described by Carter et al, in which men with early prostate cancer who are almost inevitably going to have radical treatment, choose to delay such therapy. 1
Nail varnish allergy with far-reaching consequences
Authors: C. LIDEN, M. BERG, G. FARM, K. WRANGSJO
Journal: British Journal of Dermatology (1993)

Contact allergy to nail varnish is well-known, and toluene-sulphonamide formaldehyde resin (TSAfr) was identified as the main allergen in 1943. During the period October 1989-December 1991 we identified 18 cases of contact allergy to nail varnish. The aim of the study was to describe the clinical picture, patch-test results, course and socio-medical consequences. Seventeen of the 18 patients were patch-test positive to TSAfr and 17/18 were positive to their own nail varnishes. Fourteen of the 18 were also positive to one or more substances in the standard patch-test series. The lesions were scattered, involving the face, eyelids, neck and hands. Periungual lesions were recorded in 11/18. The dermatitis resolved within a few weeks when the use of nail varnish was stopped. The socio-medical consequences of contact allergy to nail varnish had been severe: sick leave (nine cases), hospitalization (four cases), cessation of visual-display-unit (VDU) work (two cases), and job-loss (two cases). Our conclusions are that contact allergy to nail varnish and TSAfr is common; the socio-medical consequences may be severe; periungual lesions occur more frequently than previously stated, and the presence of other contact allergies makes the diagnosis easy to miss. TSAfr should be included in the standard patch-test series and patients should also be tested with their own nail varnishes. The study illustrates the need for mandatory declaration of the ingredients of cosmetics, as is required in the U.S.A.
Carboplatin Plus Paclitaxel Versus Carboplatin Plus Pegylated Liposomal Doxorubicin As First-Line Treatment for Patients With Ovarian Cancer: The MITO-2 Randomized Phase III Trial
Authors: Sandro Pignata, Giovanni Scambia, Gabriella Ferrandina, Antonella Savarese, Roberto Sorio, Enrico Breda, Vittorio Gebbia, Pietro Musso, Luigi Frigerio, Pietro Del Medico, Alessandra Vernaglia Lombardi, Antonio Febbraro, Paolo Scollo, Antonella Ferro, Stefano Tamberi, Alba Brandes, Alberto Ravaioli, Maria Rosaria Valerio, Enrico Aitini, Donato Natale, Laura Scaltriti, Stefano Greggi, Carmela Pisano, Domenica Lorusso, Vanda Salutari, Francesco Legge, Massimo Di Maio, Alessandro Morabito, Ciro Gallo, Francesco Perrone
Journal: Journal of Clinical Oncology (2011)

Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy.Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS.Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles.Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.
Akt1/protein kinase B is critical for ischemic and VEGF-mediated angiogenesis
Authors: E. Ackah
Journal: Journal of Clinical Investigation (2005)

Akt, or protein kinase B, is a multifunctional serine-threonine protein kinase implicated in a diverse range of cellular functions including cell metabolism, survival, migration, and gene expression. However, the in vivo roles and effectors of individual Akt isoforms in signaling are not explicitly clear. Here we show that the genetic loss of Akt1, but not Akt2, in mice results in defective ischemia and VEGF-induced angiogenesis as well as severe peripheral vascular disease. Akt1 knockout (Akt1–/–) mice also have reduced endothelial progenitor cell (EPC) mobilization in response to ischemia, and reintroduction of WT EPCs, but not EPCs isolated from Akt1–/– mice, into WT mice improves limb blood flow after ischemia. Mechanistically, the loss of Akt1 reduces the basal phosphorylation of several Akt substrates, the migration of fibroblasts and ECs, and NO release. Reconstitution of Akt1–/– ECs with Akt1 rescues the defects in substrate phosphorylation, cell migration, and NO release. Thus, the Akt1 isoform exerts an essential role in blood flow control, cellular migration, and NO synthesis during postnatal angiogenesis.
Influence of treatment delay on infarct size and clinical outcome in patients with acute myocardial infarction treated with primary angioplasty
Authors: Aylee L Liem, Arnoud W.J van ‘t Hof, Jan C.A Hoorntje, Menko-Jan de Boer, Harry Suryapranata, Felix Zijlstra
Journal: Journal of the American College of Cardiology (1998)
Myosin light chain kinase occurs in bullfrog sympathetic neurons and may modulate voltage-dependent potassium currents
Authors: Takashi Akasu, Masaaki Ito, Takashi Nakano, Carla R. Schneider, Mark A. Simmons, Toshio Tanaka, Takayuki Tokimasa, Masami Yoshidat
Journal: Neuron (1993)
Chronic Hyperglycemia Attenuates Coronary Collateral Development and Impairs Proliferative Properties of Myocardial Interstitial Fluid by Production of Angiostatin
Authors: Dorothee Weihrauch, Nicole L. Lohr, Boris Mraovic, Lynda M. Ludwig, William M. Chilian, Paul S. Pagel, David C. Warltier, Judy R. Kersten
Journal: Circulation (2004)

Background— Development of coronary collateral vessels is impaired in patients with diabetes mellitus. We tested the hypothesis that hyperglycemia alone attenuates collateral development and abolishes proliferative properties of myocardial interstitial fluid (MIF) by enhancing expression of matrix metalloproteinases (MMP) and angiostatin. Methods and Results— Chronically instrumented dogs were randomly assigned to receive an infusion of normal saline (control; n=9) or 70% dextrose in water to increase blood glucose to 350 to 400 mg/dL for 8 h/d (hyperglycemia; n=7) in the presence or absence (sham; n=9) of brief (2 minutes), repetitive coronary artery occlusions (1/h; 8/d for 21 days). Collateral perfusion increased to 41±11% and 49±6% of normal zone flow in control dogs on days 14 and 21 ( P &lt;0.05) but remained unchanged over 21 days in hyperglycemic and sham dogs (12±3% and 13±3%, respectively). A progressive reduction of the postocclusive peak reactive hyperemic response was also observed in control dogs (16±1 to 10±1 Hz · 10 2 on days 1 and 21, respectively) but not in hyperglycemic (17±2 to 20±2) or sham (17±2 to 16±1) dogs. Endothelial cell tube formation was produced by MIF obtained from control dogs but not hyperglycemic or sham dogs. Coincubation of MIF from hyperglycemic dogs with an angiostatin antibody restored endothelial cell tube formation. MMP-9 activity and expression of angiostatin were increased in dogs receiving exogenous glucose compared with controls Conclusions— Chronic hyperglycemia abolishes development of coronary collateral vessels by increasing MMP-9 activity and angiostatin expression in dogs.
Stress and Women Physicians
Authors: Nell-Pape Waring
Journal: JAMA (1991)

Bowman and Allen have arranged and organized the now considerable body of information, observation, and comment that bears on women in medicine and in training for medicine into the following chapters: "Women in Medical School and Academia," "Specialty Choices," "Productivity," "Practice Characteristics," "Mental Health Status," "Women Physicians' Way of Healing," "Physician Stress," "Female Physician Stress," "Physician Marriage and Dual Career Couples," "Childbearing," "Child-Rearing," "Stress Prevention and Management," and "The Future." Unfortunately, the book is not well edited. Parts (for example, the "Overview") are so poorly written that the critical reader may be distracted by a desire to copyedit. Nevertheless, there are offsetting merits. The described "studies" are summarized (in some cases tabulated) and presented as critically as they can be, in many cases with considerable insight and on occasion gallows humor. For example, on page 80 the author remarks that depression is so common in both male and female physicians
ACUTE DELIRIOUS MANIA
Authors: HUGH F. JARVIE, MARTIN C. HOOD
Journal: American Journal of Psychiatry (1952)

1. A case of acute delirious mania (Bell's mania) is described. 2. It is regarded as an affective reaction with greater affinity to the fulminating agitated depressive state than to the manic phase of manic-depressive psychosis. 3. The underlying physio-pathological mechanisms that lead to death in this malignant form of psychosis are discussed. 4. The administration of electric convulsive therapy in the early stages of the illness is advocated.