tbuckley/cabot-search huggingface dataset:
Assessment of perfusion MRI-derived parameters in evaluating and predicting response to antiangiogenic therapy in patients with newly diagnosed glioblastoma
Authors: E. Essock-Burns, J. M. Lupo, S. Cha, M.-Y. Polley, N. A. Butowski, S. M. Chang, S. J. Nelson
Journal: Neuro-Oncology (2010)

The paradigm for treating patients with glioblastoma multiforme (GBM) is shifting from a purely cytotoxic approach to one that incorporates antiangiogenic agents. These are thought to normalize the tumor vasculature and have shown improved disease management in patients with recurrent disease. How this vascular remodeling evolves during the full course of therapy for patients with newly diagnosed GBM and how it relates to radiographic response and outcome remain unclear. In this study, we examined 35 patients who were newly diagnosed with GBM using dynamic susceptibility contrast (DSC) MRI in order to identify early predictors of radiographic response to antiangiogenic therapy and to evaluate changes in perfusion parameters that may be predictive of progression. After surgical resection, patients received enzastaurin and temozolomide, both concurrent with and adjuvant to radiotherapy. Perfusion parameters, peak height (PH) and percent recovery, were calculated from the dynamic curves to assess vascular density and leakage. Six-month radiographic responders showed a significant improvement in percent recovery between baseline and 2 months into therapy, whereas 6-month radiographic nonresponders showed significantly increased PH between baseline and 1 month. At 2 months into therapy, percent recovery was predictive of progression-free survival. Four months prior to progression, there was a significant increase in the standard deviation of percent recovery within the tumor region. DSC perfusion imaging provides valuable information about vascular remodeling during antiangiogenic therapy, which may aid clinicians in identifying patients who will respond at the pretherapy scan and as an early indicator of response to antiangiogenic therapy.
Huntington's Disease: Advocacy Driving Science
Authors: Nancy S. Wexler
Journal: Annual Review of Medicine (2011)

My mother, Leonore, was diagnosed with Huntington's disease (HD) in 1968 at age 53. I was 23, my sister Alice 26, and our father, Milton Wexler, 60 years old. The same year, our father created the Hereditary Disease Foundation (HDF), dedicated to finding treatments and cures for HD. HD is an autosomal dominant, neurodegenerative disorder. Alice and I each have a 50% chance of inheriting and dying from the disorder. Over the past 43 years, we have been proud to change the face of science. Through Milton Wexler Interdisciplinary Workshops, judicious funding, and focusing on innovation and creativity, the HDF is an integral partner in key discoveries. The HDF recruited and supported &gt;100 scientists worldwide who worked together as the Huntington's Disease Collaborative Research Group in a successful ten-year search for the HD gene. We found a DNA marker for the HD gene in 1983—the first marker to be found when the chromosomal location was unknown. We isolated the HD gene itself a decade later. These breakthroughs helped launch the Human Genome Project. We supported creating the first mouse model of HD and many other model systems. Currently, we focus on gene silencing, among other approaches, to create new treatments and cures.
Role of nerve growth factor and tropomyosin receptor kinase A in the pathogenesis of osteoarthritis. Might nerve growth factor be the link interwinding obesity and osteoarthritis?
Authors: Florenzo Iannone, Simone Perniola, Giuseppe Lopalco, Luca Cantarini, Giovanni Lapadula
Journal: Annals of the Rheumatic Diseases (2015)

We read with interest the paper by Nwosu et al 1 recently published in Annals of the Rheumatic Diseases . They clearly provided evidence that blocking tropomyosin receptor kinase A (TrkA), the p140 high-affinity receptor of nerve growth factor (NGF), by a selective TrkA inhibitor AR786 relieves pain in two different rat models of osteoarthritis (OA). A reduction of synovitis was also shown by histopathology, suggesting that NGF inhibition exerted its effect at peripheral level on extraneural tissues. Authors concluded that inhibition of NGF activity might be an effective strategy as treatment of OA pain. Indeed, NGF may have pleiotropic effects, and we would like to speculate on the possible role played by NGF and its counter-receptor …
Changes in False Lumen After Transluminal Stent-Graft Placement in Aortic Dissections
Authors: Hitoshi Kusagawa, Takatsugu Shimono, Masaki Ishida, Tomoaki Suzuki, Fuyuhiko Yasuda, Uhito Yuasa, Koji Onoda, Isao Yada, Tadanori Hirano, Kan Takeda, Noriyuki Kato
Journal: Circulation (2005)

Background— Transluminal stent-graft placements (TSGPs) are a new, less invasive procedure now recognized as the choice for aortic disease repair. Treatment of aortic dissections with TSGPs has resulted in good early results, but the long-term results and changes in the false lumen have not been elucidated in detail. Methods and Results— TSGPs were performed in 49 patients with primary tears in their descending aortas, and the follow-up period ranged from 4 months to 6 years. The patients were divided into 32 acute-onset and 17 chronic dissections; of the acute-onset cases, there were 15 Stanford type A retrograde dissections. Periodic enhanced spiral CT was conducted after TSGP. The false lumen in the ascending aorta in 14 (93%) of the Stanford type A cases was obliterated completely within 3 months. The CT study was continued for &gt;2 years for 17 acute-onset dissection and 11 chronic dissection patients. The average false lumen diameters of the proximal, middle, and distal descending aorta before treatment were 15.9, 16.2, and 15.6 mm in the acute-onset dissection group and 28.1, 25.2, and 21.0 mm in the chronic dissection group, respectively. The false lumen diameters 2 years after treatment were 3.0, 3.7, and 3.1 mm in the acute-onset dissection group and 10.6, 10.5, and 11.9 mm in the chronic dissection group, respectively. Two years after TSGPs, the false lumen of the thoracic aorta totally disappeared in 76% of the acute-onset dissection group and 36% of the chronic dissection group. No cases showed rupture after TSGP. Conclusions— Complete obliteration of the false lumen is more likely in acute-onset cases than in chronic cases.
Aberrant accumulation of p53 associates with Ki67 and mitotic count in benign skin lesions
Authors: Y. SOINI, D. KAMEL, P. PÄÄKKÖ, V.-P. LEHTO, A. OIKARINEN, K. VÄHÄKANGAS
Journal: British Journal of Dermatology (2006)

Journal Article Aberrant accumulation of p53 associates with Ki67 and mitotic count in benign skin lesions Get access Y. SOINI, Y. SOINI Department of Pathology, University of Oulu, Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar D. KAMEL, D. KAMEL Department of Pathology, University of Oulu, Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar P. PÄÄKKÖ, P. PÄÄKKÖ Department of Pathology, University of Oulu, Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar V.‐P. LEHTO, V.‐P. LEHTO Department of Pathology, University of Oulu, Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar A. OIKARINEN, A. OIKARINEN Dermatology, University of Oulu, Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar K. VÄHÄKANGAS K. VÄHÄKANGAS Pharmacology and Toxicology, University of Oulu, Oulu, Finland Dr K. Vähäkangas, Department of Pharmacology and Toxicology, University of Oulu, Kajaanintie 52 D, SF‐90220 Oulu, Finland. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 4, 1 October 1994, Pages 514–520, https://doi.org/10.1111/j.1365-2133.1994.tb08552.x Published: 01 October 1994 Article history Accepted: 17 February 1994 Published: 01 October 1994
Sensory Gating Deficits Assessed by the P50 Event-Related Potential in Subjects With Schizotypal Personality Disorder
Authors: K S Cadenhead, G A Light, M A Geyer, D L Braff
Journal: American Journal of Psychiatry (2000)

The schizophrenia spectrum includes individuals with schizophrenia, their relatives, and individuals with schizotypal personality disorder. Subjects in the schizophrenia spectrum have disorders of attention, cognition, and information processing. Attention and information processing can be assessed by testing suppression of the P50 event-related potential; the amplitude of the P50 wave is measured in response to each of two auditory clicks. In normal subjects, the P50 wave following the second click is suppressed, or "gated." Schizophrenic patients and their relatives show less suppression of the second P50 wave. Deficits in P50 suppression have high heritability and show linkage to the alpha-7 subunit of the nicotinic cholinergic receptor gene in families with schizophrenia, suggesting that deficits in P50 suppression are trait markers for gating abnormalities in schizophrenia spectrum subjects. Although schizotypal subjects have been shown to have deficits in sensorimotor gating as measured by prepulse inhibition, to the authors' knowledge P50 sensory gating in schizotypal personality disorder has yet to be reported.P50 suppression in 26 subjects with schizotypal personality disorder and 23 normal subjects was assessed through auditory conditioning and testing.The subjects with schizotypal personality had significantly less P50 suppression than did the normal subjects.Subjects with schizotypal personality disorder may have trait-linked sensory gating deficits similar to those in patients with schizophrenia and their relatives. Because these subjects may manifest sensory gating deficits without overt psychotic symptoms, it is likely that these deficits represent a core cognitive dysfunction of the schizophrenia spectrum.
Where are all the genes?
Authors: Jeffrey C. Schank
Journal: Behavioral and Brain Sciences (2002)

Andrews et al. argue for adaptationism in cognitive research. However, the problem of evolvability brings into question the number of genes required for the evolution of cognitive mechanisms. Are there enough? Also, greater consideration should be given to alternative vicarious selection processes, which may produce cognitive mechanisms. Finally, identifying constraints with optimality arguments is more difficult than the authors think.
Bronchodilator tolerance: the impact of increasing bronchoconstriction
Authors: J.M. Wraight, R.J. Hancox, G.P. Herbison, J.O. Cowan, E.M. Flannery, D.R. Taylor
Journal: European Respiratory Journal (2003)

Chronic exposure to β‐agonists causes tolerance to their bronchodilator effects, which is best demonstrated during acute bronchoconstriction. The aim of the present study was to assess whether tolerance becomes more evident with increasing bronchoconstriction, as might occur in acute asthma. In a randomised, double-blind, placebo-controlled, crossover study comprising 15 patients, the treatments were salbutamol 400 µg q.i.d . or placebo given via Diskhaler® for 28 days with a 2‐week washout between treatments. Patients attended on days 14, 21 and 28. Bronchoconstriction was induced on two of these three occasions to achieve a reduction in the forced expiratory volume in one second (FEV 1 ) of 0 (no methacholine), 15 and 30% (using methacholine) in a randomised order. Immediately after this, salbutamol 100 µg, 100 µg and 200 µg was inhaled at 0, 5, and 10 min. FEV 1 was measured over 40 min. Dose/response curves were plotted and values for the area under the curve (AUC) 0–40 FEV 1 were compared between treatments and by degree of bronchoconstriction. Regular salbutamol resulted in attenuation of the acute response to β‐agonist, which was increasingly evident with greater bronchoconstriction. With a reduction in FEV 1 of 0, 15 and 30%, the AUC 0–40 FEV 1 with salbutamol were 11.2, −14.6 and −35.7% respectively, compared to placebo. There was a linear relationship between the magnitude of bronchoconstriction and the between-treatment differences in AUC 0–40 FEV 1 . Increasing bronchoconstriction conferred greater susceptibility to the effects of bronchodilator tolerance.
Disruptive T cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

A study on page 239 shows that death-inducing T cells kill smooth muscle cells in atherosclerotic plaques. Sato et al. show that this lethal T cell activity is heightened in patients with heart disease, which could destabilize the plaques in these patients and make them more prone to rupture.






Figure 1

TRAIL-expressing CD4+ T cells trigger apoptosis of vascular smooth muscle cells (red) in atherosclerotic plaques




The narrowing of arteries is a natural process caused by the gradual deposition of fat and cholesterol into artery walls. The buildup of arterial plaques (atherosclerosis) is a long-term process that, for some, culminates in acute coronary syndromes (ACSs) such as heart attack and cardiac arrest. These acute attacks are caused by the sudden rupture of atherosclerotic plaques—an event that may happen more readily in some individuals than in others.

Plaques that contain immune cells such as macrophages and T cells are the most vulnerable to rupture, although the mechanism behind this observation is not well understood. Now, Sato and colleagues show that CD4+ T cells that infiltrate atherosclerotic plaques trigger the death of vascular smooth muscle cells (VSMCs), a process proposed to destabilize the plaques.

The plaque-infiltrating T cells expressed high levels of TRAIL, a death receptor normally used by T cells and NK cells to destroy cancerous cells. The expression of this receptor was required for T cells to induce apoptosis in VSMCs (which expressed the TRAIL receptor DR5) both in vitro and in vivo. CD4+ T cells from patients with ACS expressed higher levels of TRAIL when activated and were more adept at triggering VSMC apoptosis in vitro compared with T cells from healthy individuals, possibly explaining why these individuals developed acute disease while others were spared. What causes plaque-residing VSMCs to express DR5 and why T cells infiltrate the plaques in some individuals is not yet known.

These results demonstrate that the TRAIL pathway—previously thought to induce death only in cancer cells—can also trigger apoptosis in nontransformed cells. A recombinant form of TRAIL is currently in clinical trials for the treatment of certain cancers, a therapeutic approach that might need reevaluation in light of its potential negative effects on patients with atherosclerosis.
Characterization of cardiac sarcoplasmic reticulum dysfunction during short-term, normothermic, global ischemia.
Authors: S Krause, M L Hess
Journal: Circulation Research (1984)

It has been proposed that breakdown of the excitation-contraction coupling system plays a pivotal role in myocardial dysfunction during the course of acute ischemia. We tested this hypothesis by characterizing the function of the sarcoplasmic reticulum at pH 7.1 and 6.4 after 7.5, 15, and 30 minutes of canine normothermic global ischemia. At pH 7.1, whole heart homogenate sarcoplasmic reticulum demonstrated a 49% depression of oxalate-supported calcium uptake at 7.5 minutes of ischemia, which progressed to 85% at 30 minutes of ischemia. At pH 6.4, control homogenate calcium uptake rates were significantly depressed, accompanied by a further depression in the ischemic groups. Isolated sarcoplasmic reticulum calcium uptake mirrored the effects of the whole heart homogenate. Calcium-stimulated magnesium-dependent ATPase (calcium-ATPase) activity was significantly depressed by both ischemia and acidosis, with a decrease in the coupling ratio (mumol calcium/mumol ATP) at 15 and 30 minutes of ischemia. Acidosis (pH 6.4) significantly shifted the sarcoplasmic reticulum pCalcium-ATPase curve to the right, increasing 50% activation from pCalcium 6.0 to 5.5 and depressing the maximum velocity (pH 7.1 = 2.06 +/- 0.14; pH 6.4 = 1.41 +/- 0.05 mumol Pi/mg per min; P less than 0.01). With ischemia, there was a progressive decrease in maximal activation of the calcium-ATPase enzyme and a progressive shift in calcium sensitivity to a higher concentration. Steady state calcium uptake, in the absence of oxalate, demonstrated a similar depression after 7.5 and 15 minutes of ischemia at pH 7.1 and 6.4, associated with a significant increase in the passive permeability coefficient for calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
P1. Immunoablation with t cell depleted autologous peripheral blood stem cell rescue produces complete remission in thrombocytopenic purpura (TTP) recidivant and refractory to standard treatment
Authors: I. Espigado
Journal: Annals of the Rheumatic Diseases (2001)

Under inpatient controlled conditions 4 patients with gout and hypertension were treated with varying doses of tienilic acid, a new uricosuric diuretic. Plasma urate levels were reduced by an average of 50% in association with significantly increased urinary urate excretion. A twice-daily regimen was considerably more effective than a single morning dosage in reduction of plasma urate, though both regimens were equally effective in antihypertensive potency. The single daily regimen produced greater diurnal fluctuations in plasma urate and was more frequently associated with the development of acute gout attacks.
Lymphopenia as a Prognostic Factor for Overall Survival in Advanced Carcinomas, Sarcomas, and Lymphomas
Authors: Isabelle Ray-Coquard, Claire Cropet, Martine Van Glabbeke, Catherine Sebban, Axel Le Cesne, Ian Judson, Olivier Tredan, Jaap Verweij, Pierre Biron, Inthidar Labidi, Jean-Paul Guastalla, Thomas Bachelot, David Perol, Sylvie Chabaud, Pancras C.W. Hogendoorn, Philippe Cassier, Armelle Dufresne, Jean-Yves Blay
Journal: Cancer Research (2009)

Abstract Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its effect on relapse and survival is uncertain. Its prognostic value for survival was analyzed in three databases of previously reported prospective multicenter studies: (a) FEC chemotherapy in metastatic breast carcinoma; (b) CYVADIC in advanced soft tissue sarcoma (European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group 62791); and (c) prospective, consecutive phase III studies of aggressive diffuse large-cell non–Hodgkin's lymphomas conducted at Centre Léon Bérard between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia of &amp;lt;1,000/μL before treatment was constant among the series: 25%, 24%, and 27%, respectively. Lymphopenia was significantly more frequent (P &amp;lt; 0.05) in metastatic breast cancer patients with performance status (PS) of &amp;gt;1, non–Hodgkin's lymphoma patients with international prognostic index (IPI) of &amp;gt; 0, and advanced soft tissue sarcoma and metastatic breast cancer patients with bone metastases. Inunivariate analysis, lymphopenia of &amp;lt;1,000/μL significantly correlated to overall survival in patients with metastatic breast cancer (median, 10 versus 14 mo; P &amp;lt; 0.0001), advanced soft tissue sarcoma (median, 5 versus 10 months; P &amp;lt; 0.01), and non–Hodgkin lymphoma (median, 11 versus 94 months; P &amp;lt; 0.0001). In multivariate analysis (Cox model), lymphopenia was an independent prognostic factor for overall survival in metastatic breast cancer [RR (relative risk), 1.8; 95% CI (confidence interval), 1.3–2.4] along with liver metastases and PS; in advanced soft tissue sarcoma (RR, 1.46; 95% CI, 1.0–2.1) along with liver metastases, lung metastases, and PS; and in non–Hodgkin's lymphoma (RR, 1.48; 95% CI, 1.03–2.1) along with IPI. Our findings show that lymphopenia is an independent prognostic factor for overall and progression-free survival in several cancers. [Cancer Res 2009;69(13):5383–91]
Expression of human sperm protein 17 in melanophages of cutaneous melanocytic lesions
Authors: B. Franceschini, F. Grizzi, P. Colombo, G. Soda, K. Bumm, P.L. Hermonat, M. Monti, N. Dioguardi, M. Chiriva-Internati
Journal: British Journal of Dermatology (2004)

Journal Article Expression of human sperm protein 17 in melanophages of cutaneous melanocytic lesions Get access B. Franceschini, B. Franceschini Scientific DirectionFondazione ‘Michele Rodriguez’, Istituto Scientifico per le Misure Quantitative in Medicina, Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar F. Grizzi, F. Grizzi Scientific DirectionFondazione ‘Michele Rodriguez’, Istituto Scientifico per le Misure Quantitative in Medicina, Milan, Italy Correspondence: F. Grizzi E‐mail: fabio.grizzi@humanitas.it Search for other works by this author on: Oxford Academic Google Scholar P. Colombo, P. Colombo Pathology Department Search for other works by this author on: Oxford Academic Google Scholar G. Soda, G. Soda Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza’, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar K. Bumm, K. Bumm Friedrich‐Alexander University Medical School, University of Erlangen‐Nurnberg, Erlangen‐Nurnberg, Germany Search for other works by this author on: Oxford Academic Google Scholar P.L. Hermonat, P.L. Hermonat University of Arkansas Medical Sciences, Little Rock, AR, U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. Monti, M. Monti Dermatology Unit, Istituto Clinico Humanitas, 20089 Rozzano, Milan, ItalyUniversity of Milan, Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar N. Dioguardi, N. Dioguardi Scientific DirectionFondazione ‘Michele Rodriguez’, Istituto Scientifico per le Misure Quantitative in Medicina, Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar M. Chiriva‐Internati M. Chiriva‐Internati Texas Tech University Health Science Center, Department of Microbiology and Immunology, Lubbock, TX, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 150, Issue 4, 1 April 2004, Pages 780–782, https://doi.org/10.1111/j.0007-0963.2004.05887.x Published: 01 April 2004