tbuckley/cabot-search huggingface dataset:
Cost of Migration: Invasion of Malignant Gliomas and Implications for Treatment
Authors: A. Giese, R. Bjerkvig, M.E. Berens, M. Westphal
Journal: Journal of Clinical Oncology (2003)

Tumors of glial origin consist of a core mass and a penumbra of invasive, single cells, decreasing in numbers towards the periphery and still detectable several centimeters away from the core lesion. Several decades ago, the diffuse nature of malignant gliomas was recognized by neurosurgeons when super-radical resections using hemispherectomies failed to eradicate these tumors. Local invasiveness eventually leads to regrowth of a recurrent tumor predominantly adjacent to the resection cavity, which is not significantly altered by radiation or chemotherapy. This raises the question of whether invasive glioma cells activate cellular programs that render these cells resistant to conventional treatments. Clinical and experimental data demonstrate that glioma invasion is determined by several independent mechanisms that facilitate the spread of these tumors along different anatomic and molecular structures. A common denominator of this cellular behavior may be cell motility. Gene-expression profiling showed upregulation of genes related to motility, and functional studies demonstrated that cell motility contributes to the invasive phenotype of malignant gliomas. There is accumulating evidence that invasive glioma cells show a decreased proliferation rate and a relative resistance to apoptosis, which may contribute to chemotherapy and radiation resistance. Interestingly, interference with cell motility by different strategies results in increased susceptibility to apoptosis, indicating that this dynamic relationship can potentially be exploited as an anti-invasive treatment paradigm. In this review, we discuss mechanisms of glioma invasion, characteristics of the invasive cell, and consequences of this cellular phenotype for surgical resection, oncologic treatments, and future perspectives for anti-invasive strategies.
High nontransferrin bound iron levels and heart disease in thalassemia major
Authors: Antonio Piga, Filomena Longo, Lorena Duca, Simona Roggero, Tiziana Vinciguerra, Roberto Calabrese, Chaim Hershko, Maria Domenica Cappellini
Journal: American Journal of Hematology (2008)

Abstract Although the presence of nontransferrin bound plasma iron (NTBI) in transfusional iron overload is well documented, knowledge about its clinical significance is limited. We assessed NTBI levels in a large and homogeneous series of thalassemia patients on regular transfusion and chelation and explored the hypothesis that NTBI levels may be associated with relevant clinical outcomes: in particular, heart disease. Among 174 patients with thalassemia major and intermedia, we showed the presence NTBI in 145 of 174 or 83.3% of cases. NTBI levels correlated with transferrin saturation, age, and ALT, and not with serum ferritin or liver iron concentrations. At a multiple regression analysis, transferrin saturation and heart disease but not age was independent predictors of NTBI. Patients with heart disease had NTBI levels significantly higher than those without. All patients with heart disease had transferrin saturation above 70%, and all were NTBI positive. Conversely, none of the patients without NTBI and/or with transferrin saturation less than 70% had preclinical or clinical heart disease. To our knowledge, this is the first documentation of a link between the presence of NTBI in thalassemic patients with transfusional iron overload and heart disease. Further investigation from these preliminary findings may clarify whether NTBI assessment may have a role in evaluating the risks and optimizing treatment for transfusion‐dependent patients. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.
Is American Bioethics Lost in the Woods?
Authors: Michael Cook
Journal: PLoS Medicine (2005)

The case report by Nautiyal et al. [1] is an instructive reminder that the fi rst episode of an acute painful Horner Syndrome should prompt imaging of the ipsilateral internal carotid artery, since carotid dissection (as well as other conditions, such as high-grade stenosis) needs to be ruled out.Unfortunately, the authors perpetuate the extremely common misconception that enophthalmos accompanies ptosis and miosis in human Horner Syndrome.It is only an illusion of enophthalmos caused by the ptosis.This is evident in the left eye of their patient in Figure 1 of the case report.Actual measurement with exophthalmometry clearly demonstrates the lack of enophthalmos.As stated by Loewenfeld ([2], p. 1139), "Animals such as cats, rats, or dogs have enophthalmos on the side of the sympathetic lesion.But in man, the enophthalmos is only apparent.The small palpebral fi ssure makes the eye look sunken in on the affected side, but the position of the globe in the orbit remains virtually unchanged.This has been found by all workers who have measured the supposed enophthalmos objectively."Loewenfeld cites four supportive references.Thompson and Miller ([3], p. 964) provide four additional references that the enophthalmos "is apparent rather than real.
Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification.
Authors: I Jialal, S M Grundy
Journal: Journal of Clinical Investigation (1991)

Several lines of evidence indicate that the oxidative modification of low density lipoproteins (LDL) may provide an important link between plasma LDL and the genesis of the atherosclerotic lesion. Ascorbate is an important water-soluble, chain-breaking antioxidant in humans. Probucol, a lipid-soluble antioxidant drug has been shown to retard the progression of atherosclerosis. The aim of the present study was to compare the effects of probucol and physiologic levels of ascorbate on the oxidative modification of LDL in both a cell-free (2.5 microM Cu++ in phosphate-buffered saline) and cellular system (human monocyte macrophages in Ham's F-10 medium). Both ascorbate and probucol inhibited the oxidative modification of LDL in both systems to a similar degree as evidenced by the thiobarbituric acid-reacting substance activity, electrophoretic mobility, and degradation by macrophages. However, whereas co-incubation with physiologic levels of ascorbate resulted in a substantial preservation of the alpha-tocopherol, gamma-tocopherol, and beta-carotene of the LDL, probucol in concentrations ranging from 10 to 80 microM failed to protect these antioxidants. Thus, in addition to being as potent as probucol in inhibiting the oxidation of LDL, ascorbate in contrast preserves the endogenous antioxidants in the LDL.
Heart Disease in Infants, Children and Adolescents
Authors: Antoni M. Diehl
Journal: JAMA (1968)

Seventy-five authors, each having special knowledge or interest in his respective subject, have contributed to this multi-authored pediatric cardiology textbook. The continuous broadening of the horizons of the scope of pediatric cardiology make the subject too large for any one person to become and remain competent and authoritative in all of the modalities. The coeditors, Drs. Moss and Adams, have uniquely selected the text material and melded the contributors' manuscripts into a meaningful format which makes the contents readable with repetition kept to a minimum. The stature of the editors and the contributors and their years of experience in the field produce information hitherto unachieved.  The chapters represent a synopsis of data, ideas, and views culled from the literature in addition to original work yet unpublished. Many of the authors have included subject material experienced at their respective medical centers. In certain areas within the text conflicts of opinions exist.
Comparison of long-term drug survival and safety of biologic agents in patients with psoriasis vulgaris
Authors: R. Gniadecki, B. Bang, L.E. Bryld, L. Iversen, S. Lasthein, L. Skov
Journal: British Journal of Dermatology (2014)

Drug survival (time to drug discontinuation) has recently emerged as an important parameter reflecting the long‐term therapeutic performance in a real‐life setting. Biologic drug survival in psoriasis is mainly limited by a gradual loss of efficacy over time. Previous studies have been limited by small patient population size and short observation times and yielded discrepant survival times for different biologics. To calculate the long‐term drug survival for adalimumab, etanercept, infliximab and ustekinumab in a large cohort of real‐life patients with psoriasis vulgaris and to analyse the factors that influence drug survival. Data were extracted from the prospective registry DERMBIO covering all patients with psoriasis vulgaris treated with biologic agents in the academic centres in Denmark. Drug survival was analysed using the Kaplan–Meier method. The influence of different covariates on drug survival was analysed by Cox regression. Included in the analysis were 1867 treatment series (adalimumab n =774, etanercept n =449, infliximab n =253, ustekinumab n =391) administered in 1277 patients for up to 10 years. Drug survival was significantly longer for ustekinumab than for anti‐tumour necrosis factor (TNF)‐α agents (P <0·001). Etanercept had the shortest survival time [median survival 30 months, 95% confidence interval (CI) 25·1–34·9] whereas adalimumab and infliximab had comparable survival rates (59 months, 95% CI 45·6–72·4; 44 months, 95% CI 33–54·9, respectively). Survival was longer in men [odds ratio (OR) 1·51, 95% CI 1·31–1·74 vs. women] and in patients who had not previously received any biologic agent (OR 1·24, 95% CI 1·05–1·46). Loss of efficacy accounted for 67% of all drug discontinuations. Ustekinumab has a significantly longer drug survival than the anti‐TNF‐α agents. Switching from one biologic to another is associated with an impairment of drug survival. Preventing loss of efficacy is a major area of medical need in the biologic therapy of psoriasis and the strategies that improve drug survival should be further investigated.
Changes in protein kinase C activity during histamine release from activated rat mast cells
Authors: M. Kurosawa, S. Kobayashi
Journal: Allergy (1989)

Rat mast cells were challenged with compound 48/80 or calcium ionophore A23187, and protein kinase C activity in the cell pellets and the amount of histamine release into the supernatant were measured. After stopping the reaction, rat mast cells were lysed in a medium which prevents alterations in phosphorylation and dephosphorylation during sample processing. Histamine was significantly released from compound 4–8/80‐stimulated mast cells at 30 s after the stimulation. In parallel with this, protein kinase C activity in the cell pellets increased at 30 s and 1 min and returned to basal value 3 min after the stimulation. When mast cells were incubated with various concentrations of 48/80 for 30 s, the amount of histamine release and protein kinase C activity increased dependently on the concentration of 48/80. Significant histamine release from A23187‐stimulated mast cells was found at 1 min after the stimulation. Also protein kinase C activity in the cell pellets increased at 1 min and returned to basal value 5 min after the stimulation. A reduction of cytosolic protein kinase C activity was observed upon 48/80 treatment in a time‐ and concentration‐dependent manner. Further, staurosporine, a potent inhibitor of protein kinase C, inhibited 48/80‐induced histamine release in parallel with the inhibition of protein kinase C activity. These findings suggest that transient increase of protein kinase C activity may be involved in the mast cell activation process.
Burden of Systolic and Diastolic Ventricular Dysfunction in the Community
Authors: Margaret M. Redfield, Steven J. Jacobsen, John C. Burnett, Douglas W. Mahoney, Kent R. Bailey, Richard J. Rodeheffer
Journal: JAMA (2003)

<h3>Context</h3> Approximately half of patients with overt congestive heart failure (CHF) have diastolic dysfunction without reduced ejection fraction (EF). Yet, the prevalence of diastolic dysfunction and its relation to systolic dysfunction and CHF in the community remain undefined. <h3>Objectives</h3> To determine the prevalence of CHF and preclinical diastolic dysfunction and systolic dysfunction in the community and determine if diastolic dysfunction is predictive of all-cause mortality. <h3>Design, Setting, Participants</h3> Cross-sectional survey of 2042 randomly selected residents of Olmsted County, Minnesota, aged 45 years or older from June 1997 through September 2000. <h3>Main Outcome Measures</h3> Doppler echocardiographic assessment of systolic and diastolic function. Presence of CHF diagnosis by review of medical records with designation as validated CHF if Framingham criteria are satisfied. Subjects without a CHF diagnosis but with diastolic or systolic dysfunction were considered as having either preclinical diastolic or preclinical systolic dysfunction. <h3>Results</h3> The prevalence of validated CHF was 2.2% (95% confidence interval [CI], 1.6%-2.8%) with 44% having an EF higher than 50%. Overall, 20.8% (95% CI, 19.0%-22.7%) of the population had mild diastolic dysfunction, 6.6% (95% CI, 5.5%-7.8%) had moderate diastolic dysfunction, and 0.7% (95% CI, 0.3%-1.1%) had severe diastolic dysfunction with 5.6% (95% CI, 4.5%-6.7%) of the population having moderate or severe diastolic dysfunction with normal EF. The prevalence of any systolic dysfunction (EF ≤50%) was 6.0% (95% CI, 5.0%-7.1%) with moderate or severe systolic dysfunction (EF ≤40%) being present in 2.0% (95% CI, 1.4%-2.5%). CHF was much more common among those with systolic or diastolic dysfunction than in those with normal ventricular function. However, even among those with moderate or severe diastolic or systolic dysfunction, less than half had recognized CHF. In multivariate analysis, controlling for age, sex, and EF, mild diastolic dysfunction (hazard ratio, 8.31 [95% CI, 3.00-23.1],<i>P</i>&lt;.001) and moderate or severe diastolic dysfunction (hazard ratio, 10.17 [95% CI, 3.28-31.0],<i>P</i>&lt;.001) were predictive of all-cause mortality. <h3>Conclusions</h3> In the community, systolic dysfunction is frequently present in individuals without recognized CHF. Furthermore, diastolic dysfunction as rigorously defined by comprehensive Doppler techniques is common, often not accompanied by recognized CHF, and associated with marked increases in all-cause mortality.
Vitamin D deficiency is associated with severity of liver disease in HIV/HCV coinfected patients
Authors: María Guzmán-Fulgencio, Mónica García-Álvarez, Juan Berenguer, M Ángeles Jiménez-Sousa, Jaime Cosín, Daniel Pineda-Tenor, Ana Carrero, Teresa Aldámiz, Emilio Alvarez, Juan Carlos López, Salvador Resino
Journal: Journal of Infection (2013)
Haemorrhage involving the central nervous system in haemophilia: account of the management of five cases.
Authors: B. M. Fessey, M. J. Meynell
Journal: BMJ (1966)

A leading article in the British Medical 7ournal (1964) empha- sized the poor prognosis for survival when haemorrhage involves the central nervous system in haemophilia.The purpose of this communication is to describe our experience with five such cases, only one of which terminated fatally, a result due largely to treatment with antihaemophilic globulin (A.H.G.).concentrates which have been available since 1958.Since 1954, at this hospital, a register has been kept of haemo- philiacs and patients with allied disorders residing in the West Midland area.Up to date we have had 191 haemophiliacs (A.H.G. (factor VIII) deficiency), 20 patients with Christmas disease (plasma thromboplastin component (P.T.C., factor IX) deficiency), and 15 with von Willebrand's disease (capillary defect with or without A.H.G. deficiency).These were diag- nosed by the thromboplastin generation test (Biggs and Douglas, 1953).The normal range of A.H.G. by the method used (Biggs, Eveling, and Richards, 1955) was 50% to 150%.During this period 306 patients over the age of 14 were admitted, with three deaths.The first, that of a man of 60, occurred from ascending pyelonephritis and uraemia following prostatectomy.The second, that of a severe haemophiliac of 45, was also from pyelonephritis and uraemia after local removal by diathermy of a malignant papilloma of the bladder.The third patient, a severe haemophiliac of 20, had a spontaneous acute subdural haemorrhage.Of the 306 admissions, five (including the patient already mentioned) had haemorrhage involving the central nervous system; four were haemophiliacs and the fifth had Christmas disease.Trauma followed by progressive increase in neuro- logical signs presents no diagnostic problem.In the absence of a history of injury we consider that headache lasting more than 12 hours is an indication for replacement therapy.We have avoided the use of routine diagnostic procedures available to patients without coagulation defects-for example, lumbar puncture, carotid angiography, and craniotomy-since we believe that any of these are capable of producing fatal haemorrhage.
Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia
Authors: Brian J. Druker, Nicholas B. Lydon
Journal: Journal of Clinical Investigation (2000)

A Protein kinase targeted.A number of these molecules are broad-spectrum kinase inhibitors.B Staurosporine class represents examples of broad-spectrum kinase inhibitors.PCD, preclinical development.These compounds may have progressed to phase I clinical trials.
Potassium depletion increases luminal Na+/H+ exchange and basolateral Na+:CO3=:HCO3- cotransport in rat renal cortex.
Authors: M Soleimani, J A Bergman, M A Hosford, T D McKinney
Journal: Journal of Clinical Investigation (1990)

Most HCO3- reabsorption in proximal tubules occurs via electroneutral Na+/H+ exchange in brush border membranes (BBMS) and electrogenic Na+:CO3=:HCO3- cotransport in basolateral membranes (BLMS). Since potassium depletion (KD) increases HCO3- reabsorption in proximal tubules, we evaluated these transport systems using BBM and BLM vesicles, respectively, from control (C) and KD rats. Feeding rats a potassium deficient diet for 3-4 wk resulted in lower plasma [K+] (2.94 mEq/liter, KD vs. 4.47 C), and higher arterial pH (7.51 KD vs. 7.39 C). KD rats gained less weight than C but had higher renal cortical weight. Influx of 1 mM 22Na+ at 5 s (pHo 7.5, pHi 6.0, 10% CO2, 90% N2) into BLM vesicles was 44% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was DIDS sensitive, suggesting that Na+:CO3=:HCO3- cotransport accounted for the observed differences. Kinetic analysis of Na+ influx showed a Km of 8.2 mM in KD vs. 7.6 mM in C and Vmax of 278 nmol/min/mg protein in KD vs. 177 nmol/min/mg protein in C. Influx of 1 mM 22Na+ at 5 s (pHo 7.5, pHi 6.0) into BBM vesicles was 34% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was amiloride sensitive, suggesting that Na+/H+ exchange was responsible for the observed differences. Kinetic analysis of Na+ influx showed a Km of 6.2 mM in KD vs. 7.1 mM in C and Vmax of 209 nmol/min/mg protein in KD vs. 144 nmol/min/mg protein in C. Uptakes of Na(+)-dependent [3H]glucose into BBM and [14C]succinate into BLM vesicles were not different in KD and C groups, suggesting that the Na+/H+ exchanger and Na+:CO3=:HCO3- cotransporter activities were specifically altered in KD. We conclude that adaptive increases in basolateral Na+:CO3=:HCO3- cotransport and luminal Na+H+ exchange are likely responsible for increased HCO3- reabsorption in proximal tubules of KD animals.
Thoracic Spinal Cord Stimulation Reduces the Risk of Ischemic Ventricular Arrhythmias in a Postinfarction Heart Failure Canine Model
Authors: Ziad F. Issa, Xiaohong Zhou, Michael R. Ujhelyi, Josh Rosenberger, Deepak Bhakta, William J. Groh, John M. Miller, Douglas P. Zipes
Journal: Circulation (2005)

Thoracic spinal cord stimulation (SCS) is a promising therapy in treating refractory angina. This study was designed to investigate SCS with regard to the risk of arrhythmias during myocardial ischemia and its cardiac electrophysiological effects.We studied 22 dogs with healed anterior myocardial infarction (MI) and superimposed heart failure (HF) induced by rapid ventricular pacing. SCS was applied at the dorsal T1-T2 segments of the spinal cord (at 50 Hz, 0.2 ms) for 15 minutes. Transient (2-minute) myocardial ischemia was induced on 2 separate occasions (no SCS and SCS) to provoke ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation; VT/VF). Ischemic episodes were separated by 90 minutes, and dogs were randomly assigned to receive SCS or no SCS before the first or second ischemic episode. SCS reduced the occurrence of VT/VF from 59% to 23% when SCS was applied during transient myocardial ischemia (odds ratio, 0.36; 95% confidence interval, 0.1626 to 0.5646; P=0.0009). SCS also decreased sinus rate by 7.5+/-14 bpm (P=0.048), increased the PR interval by 11.1+/-14.7 ms (P=0.009), and reduced systolic blood pressure by 9.8+/-13.6 mm Hg (P=0.02).Thoracic SCS appears to protect against ischemic VT/VF in a canine model of healed MI and HF. SCS reduced sinus rate and systolic blood pressure, changes consistent with the previously known antisympathetic effect of SCS, which may have contributed to the antiarrhythmic benefits.
Abstract 1949: Receptor mediated delivery of therapeutic Fe3O4 core TiO2 shell nanoparticles
Authors: Ye Yuan, William C. Liu, Aiguo Wu, Tatjana Paunesku, Gayle E. Woloschak
Journal: Cancer Research (2012)

Abstract Our goal is to target the delivery of therapeutic nanoparticles (NPs) composed of an Fe3O4 core and a TiO2 shell (Fe@Ti NPs) to specific cancer cells and to the appropriate organelles within these cells. Controlled delivery of these therapeutic NPs could lead to the development of more effective therapies for individual types of cancer. In order to control the delivery of these Fe@Ti NPs, we have attached a small peptide that can bind Epidermal Growth Factor Receptor (EGFR) to the TiO2 molecules at the surface of the NPs. EGFR is an ideal target because it is overexpressed in epithelial type cancers, can induce its own endocytosis, and can translocate to the nucleus. We hypothesize that Fe@Ti NPs conjugated with these peptides (Fe@Ti NCs) will be able to bind EGFR resulting in improved internalization and nuclear localization of these NCs by EGFR positive cancer cells. In fact, we have shown that these NCs can indeed bind and extract EGFR from cancer cell protein extracts. Furthermore, we have shown by Flow Cytometry that EGFR positive cancer cells internalize EGFR binding Fe@Ti NCs to a greater degree than NCs displaying a scrambled peptide or bare NPs. Finally, recent experiments utilizing X-ray Fluorescence Microscopy (XFM) indicate that these EGFR binding NCs but not bare NPs can cluster with EGFR at the surface of cancer cells as well as within the cell nucleus. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1949. doi:1538-7445.AM2012-1949
Syphilitic Aortitis in Secondary Syphilis
Authors: Andreas Dietrich, Gerd G. Gauglitz, Thomas T. Pfluger, Thomas Herzinger, Markus Braun-Falco
Journal: JAMA Dermatology (2014)

Syphilitic Aortitis in Secondary Syphilis Syphilis is a mainly sexually transmitted infection that may show a variety of symptoms at various stages. Syphilitic aortitis is a knowncomplicationof tertiary syphilis and can cause aneurysmof the aorta.1 In the era of antibiotics, cardiovascular syphilis has become very rare.2 Nevertheless it can cause life-threatening or even fatal symptoms and should therefore be diagnosed at an early stage.3
LACK OF EFFECT OF THIAZIDE DIURETICS ON BONE MINERAL DENSITY IN HYPERTENSIVE ELDERLY AFRICAN AMERICAN WOMEN
Authors: Fahad Javed, Emad F. Aziz, Alexandre M. Benjo, Ramya Suryadevara, Carlos Alviar, Jorge Romero, Iffat Shaheen, Eyal Herzog, Franz Messerli
Journal: Journal of the American College of Cardiology (2010)