tbuckley/cabot-search huggingface dataset:
Development and validation of a prediction index for hand-foot skin reaction in cancer patients receiving sorafenib
Authors: G. Dranitsaris, M.D. Vincent, J. Yu, L. Huang, F. Fang, M.E. Lacouture
Journal: Annals of Oncology (2012)

BackgroundThis study describes a repeated measures prediction index to identify patients at high risk of ≥ grade 2 hand-foot skin reaction (HFSR) before each week of sorafenib therapy.MethodsData from 451 patients who received a sorafenib (400 mg bid) as part of a clinical trial were reviewed (Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125–134). Generalized estimating equations were used to develop the final risk model. A risk-scoring algorithm (range 0–58) was then derived from the final model coefficients. External validation was then carried out on a new sample of 1145 patients who received sorafenib under an expanded access program.ResultsPretreatment white blood cell count, female gender, good performance status, presence of lung and liver metastases and number of affected organs were predictors for ≥ grade 2 HFSR. A nonlinear association between HFSR risk and treatment duration was also identified where risk was maximized at week 5 followed by a gradual decline. Before each week of therapy, patients with risk scores >40 would be considered at high risk for developing ≥ grade 2 HFSR.ConclusionsThe application and planned continued refinement of this prediction tool will be an important source of patient-specific risk information for the development of moderate to severe HFSR.
Acute renal tubular and hemodynamic effects of the calcium antagonist felodipine in healthy volunteers.
Authors: P L Katzman, G F DiBona, B Hökfelt, U L Hulthén
Journal: Journal of the American Society of Nephrology (1991)

To evaluate the renal tubular effects of felodipine in a low (1.25-mg) and a high (10-mg) dose, lithium clearance was measured and related to renal hemodynamics in 10 healthy volunteers. After felodipine (1.25 mg), mean blood pressure decreased 4 mm Hg and heart rate increased 4 beats per minute. GFR and renal hemodynamics were unaltered. Natriuresis and diuresis increased and lithium clearance and fractional excretion of lithium were unchanged as compared with placebo. Felodipine (10 mg) decreased mean blood pressure 8 mm Hg; heart rate increased 16 beats per minute, and plasma catecholamines were elevated. GFR was unaltered, whereas RBF increased and renal vascular resistance decreased. Natriuresis and diuresis were further increased, and lithium clearance and fractional excretion of lithium were elevated. In conclusion, felodipine in a low dose of 1.25 mg, which did not change renal hemodynamics, had natriuretic and diuretic effects at a predominantly postproximal tubular site, whereas a high dose of 10 mg, which increased RBF and decreased renal vascular resistance, had additional natriuretic and diuretic effects in the proximal tubule.
HCCR-1 for detecting small hepatocellular carcinoma latent in a cirrhotic liver: a prospective cohort study
Authors: Peng Jirun, Guoxin Zhang, Seon-Ah Ha, Hyun Kee Kim, Jinah Yoo, Sanghee Kim, Jin Zhongtian, Cui Zhuqingqing, Youn Soo Lee, Gi Hwan Gong, Joo Hee Yoon, Hae Nam Lee, Sa Jin Kim, Tae Eung Kim, Eun Young Song, Yun Kyung Lee, Yong Gyu Park, Jin Woo Kim
Journal: Gut (2012)

We read with great interest the leading article by Tremosini and coworkers in Gut (2012 doi:10.1136/gutjnl-2011-301951) on the prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma (HCC).1 In this …
p66Shc as a switch in bringing about contrasting responses in cell growth: implications on cell proliferation and apoptosis
Authors: Sahar S Bhat, Deepak Anand, Firdous A Khanday
Journal: Molecular Cancer (2015)

p66Shc, a member of the ShcA (Src homologous- collagen homologue) adaptor protein family, is one of the three isoforms of this family along with p46Shc and p52Shc. p66Shc, a 66 kDa protein is different from the other isoforms of the ShcA family. p66Shc is the longest isoform of the ShcA family. p66Shc has an additional CH domain at the N-terminal, called the CH2 domain, which is not not present in the other isoforms. This CH2 domain contains a very crucial S36 residue which is phosphorylated in response to oxidative stress and plays a role in apoptosis. Whereas p52Shc and p46Shc are ubiquitously expressed, p66Shc shows constrained expression. This adaptor protein has been shown to be involved in mediating and executing the post effects of oxidative stress and increasing body of evidence is pinpointing to its role in carcinogenesis as well. It shows proto-oncogenic as well as pro-apoptotic properties. This multitasking protein is involved in regulating different networks of cell signaling. On one hand it shows an increased expression profile in different cancers, has a positive role in cell proliferation and migration, whereas on the other hand it promotes apoptosis under oxidative stress conditions by acting as a sensor of ROS (Reactive Oxygen Species). This paradoxical role of p66Shc could be attributed to its involvement in ROS production, as ROS is known to both induce cell proliferation as well as apoptosis. p66Shc by regulating intracellular ROS levels plays a crucial role in regulating longevity and cell senescence. These multi-faceted properties of p66Shc make it a perfect candidate protein for further studies in various cancers and aging related diseases. p66Shc can be targeted in terms of it being used as a possible therapeutic target in various diseases. This review focuses on p66Shc and highlights its role in promoting apoptosis via different cell signaling networks, its role in cell proliferation, along with its presence and role in different forms of cancers.
International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy
Authors: Markus Graefen, Pierre I. Karakiewicz, Ilias Cagiannos, David I. Quinn, Susan M. Henshall, John J. Grygiel, Robert L. Sutherland, Phillip D. Stricker, Eric Klein, Patrick Kupelian, Donald G. Skinner, Gary Lieskovsky, Bernard Bochner, Hartwig Huland, Peter G. Hammerer, Alexander Haese, Andreas Erbersdobler, James A. Eastham, Jean de Kernion, Thomas Cangiano, Fritz H. Schröder, Mark F. Wildhagen, Theo H. van der Kwast, Peter T. Scardino, Michael W. Kattan
Journal: Journal of Clinical Oncology (2002)

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification–based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low–risk group), 39% (intermediate-high–risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.
POST-OPERATIVE MYOCARDIAL INFARCTION IN ACUTE AORTIC DISSECTION PATIENTS: A REPORT FROM THE INTERNATIONAL REGISTRY OF ACUTE AORTIC DISSECTION
Authors: Ali Khoynezhad, Marco Di Eusanio, Marek Ehrlich, Brett Reece, Nimesh Desai, Thoralf Sundt, Truls Myrmel, Thomas Gleason, Alberto Forteza, Peter Oberwalder, Santi Trimarchi, Daniel Montgomery, Kim Eagle, Eric Isselbacher, Christoph Nienaber
Journal: Journal of the American College of Cardiology (2014)
Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice
Authors: Dhananjay K. Kaul, Xiao-du Liu, Hee-Yoon Chang, Ronald L. Nagel, Mary E. Fabry
Journal: Journal of Clinical Investigation (2004)

In sickle cell disease, intravascular sickling and attendant flow abnormalities underlie the chronic inflammation and vascular endothelial abnormalities. However, the relationship between sickling and vascular tone is not well understood. We hypothesized that sickling-induced vaso-occlusive events and attendant oxidative stress will affect microvascular regulatory mechanisms. In the present studies, we have examined whether microvascular abnormalities expressed in sickle transgenic-knockout Berkeley (BERK) mice (which express exclusively human α- and βS-globins with <1% γ-globin levels) are amenable to correction with increased levels of antisickling fetal hemoglobin (HbF). In BERK mice, sickling, increased oxidative stress, and hemolytic anemia are accompanied by vasodilation, compensatory increases in eNOS and COX-2, and attenuated vascular responses to NO-mediated vasoactive stimuli and norepinephrine. The hypotension and vasodilation (required for adequate oxygen delivery in the face of chronic anemia) are mediated by non-NO vasodilators (i.e., prostacyclin) as evidenced by induction of COX-2. In BERK mice, the resistance to NO-mediated vasodilators is associated with increased oxidative stress and hemolytic rate, and in BERK + γ mice (expressing 20% HbF), an improved response to these stimuli is associated with reduced oxidative stress and hemolytic rate. Furthermore, BERK + γ mice show normalization of vessel diameters, and eNOS and COX-2 expression. These results demonstrate a strong relationship between sickling and microvascular function in sickle cell disease.
The cell cycle time in the flat (avillous) mucosa of the human small intestine
Authors: N. Wright, A. Watson, A. Morley, D. Appleton, J. Marks, A. Douglas
Journal: Gut (1973)

A hyperproductive mucosal state in gluten-sensitive enteropathy has been proposed on the basis of an elevated mitotic index, but this parameter is dependent on the mitotic duration when used as an index of proliferative status. The mitotic duration was therefore measured in two control patients with normal villous mucosae and in two patients with the flat avillous mucosa of untreated gluten-sensitive enteropathy, using two different stathmokinetic techniques with vincristine. No significant difference in mitotic duration was found but values obtained for cell cycle time showed a halving in the flat mucosae. An increased rate of cell production in the small bowel mucosa of untreated gluten-sensitive enteropathy is thus confirmed.
[33] HEPATITIS C VIRUS COMPARTMENTALIZATION AND INFECTION RECURRENCE AFTER LIVER TRANSPLANTATION
Authors: S. Ramirez, A. Massaguer, J. Carrion, J. Costa, J.M. Sanchez-Tapias, C. Fontdevila, J.C. Garcia-Valdecasas, X. Forns
Journal: Journal of Hepatology (2007)
Overexpression of Molecular Chaperone Genes in Nucleomorph Genomes
Authors: Yoshihisa Hirakawa, Shigekatsu Suzuki, John M. Archibald, Patrick J. Keeling, Ken-ichiro Ishida
Journal: Molecular Biology and Evolution (2014)

Chlorarachniophytes and cryptophytes possess complex plastids that were acquired by the ingestion of a green and red algal endosymbiont, respectively. The plastids are surrounded by four membranes, and a relict nucleus, called the nucleomorph, remains in the periplastidal compartment, which corresponds to the remnant cytoplasm of the endosymbiont. Nucleomorphs contain a greatly reduced genome that possesses only several hundred genes with high evolutionary rates. We examined the relative transcription levels of the genes of all proteins encoded by the nucleomorph genomes of two chlorarachniophytes and three cryptophytes using an RNA-seq transcriptomic approach. The genes of two heat shock proteins, Hsp70 and Hsp90, were highly expressed under normal conditions. It has been shown that molecular chaperone overexpression allows an accumulation of genetic mutations in bacteria. Our results suggest that overexpression of heat shock proteins in nucleomorph genomes may play a role in buffering the mutational destabilization of proteins, which might allow the high evolutionary rates of nucleomorph-encoded proteins.
Glutamatergic Mechanisms in Schizophrenia
Authors: Guochuan Tsai, Joseph T. Coyle
Journal: The Annual Review of Pharmacology and Toxicology (2002)

Schizophrenia is a chronic, severely disabling brain disorder with symptomatic onset in early adulthood. Typical antipsychotic medications that block dopamine D2 receptors are most effective in treating the psychosis but have limited effects on the negative symptoms and cognitive impairments. Considerable research has demonstrated that noncompetitive NMDA receptor antagonists, the dissociative anaesthetic like phencyclidine and ketamine, reproduce the cardinal symptomatic features of schizophrenia. Postmortem studies reveal variable alterations in glutamate receptors and their modulators in schizophrenia. Several clinical trials indicate agents that enhance NMDA receptor function via the glycine modulatory site reduce negative and variably improve cognitive function in schizophrenics receiving typical antipsychotics. Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may participate in the pathophysiology of schizophrenia.
Catheter Ablation of Paroxysmal Atrial Fibrillation Using a 3D Mapping System
Authors: Carlo Pappone, Giuseppe Oreto, Filippo Lamberti, Gabriele Vicedomini, Maria Luisa Loricchio, Shlomo Shpun, Mariano Rillo, Maria Pia Calabrò, Andrea Conversano, Shlomo A. Ben-Haim, Riccardo Cappato, Sergio Chierchia
Journal: Circulation (1999)

We treated paroxysmal recurrent atrial fibrillation (AF) with radiofrequency (RF) catheter ablation by creating long linear lesions in the atria. To achieve line continuity, a 3D electroanatomic nonfluoroscopic mapping system was used.In 27 patients with recurrent AF, a catheter incorporating a passive magnetic field sensor was navigated in both atria to construct a 3D activation map. RF energy was delivered to create continuous linear lesions: 3 lines (intercaval, isthmic, and anteroseptal) in the right atrium and a long line encircling the pulmonary veins in the left atrium. After RF application, the atria were remapped to validate completeness of the block lines, demonstrated by late activation of the areas circumscribed by the lines. The mean procedure duration was 312+/-103 minutes (range, 187 to 495), with mean fluoroscopy time of 107+/-44 minutes (range, 32 to 185 minutes). No acute complications occurred, but 1 patient experienced early prolonged sinus pauses and received a pacemaker. During the first day, 17 patients (63%) had AF episodes, but at discharge, 25 patients were in sinus rhythm. After a follow-up of 6. 0 to 15.3 months (average, 10.5+/-3.0 months), 16 patients are asymptomatic, 3 have an almost complete disappearance of symptoms, 1 patient is improved, and 7 patients have their AF attacks unchanged.Paroxysmal recurrent drug-refractory AF can be treated by RF catheter ablation. Creation of long continuous linear lesions necessary to compartmentalize the atria is facilitated by a nonfluoroscopic electroanatomic mapping system.
Increased Error-Related Brain Activity in Pediatric Obsessive-Compulsive Disorder Before and After Treatment
Authors: Greg Hajcak, Martin E. Franklin, Edna B. Foa, Robert F. Simons
Journal: American Journal of Psychiatry (2007)

Objective: The error-related negativity is a negative deflection in the event-related potential maximal approximately 50 msec after the commission of errors. The error-related negativity is generated in the anterior cingulate cortex, and both anterior cingulate cortex hyperactivity and increased error-related brain activity have been reported in adults with obsessive-compulsive disorder (OCD). However, no study to date, to the authors’ knowledge, has examined error-related brain activity in pediatric patients with OCD, and no study has examined error-related brain activity in OCD both before and after treatment. Method: The error-related negativity was measured in 18 treatment-seeking pediatric patients with OCD and 18 age-matched comparison subjects. Of these patients, 10 returned for a second testing session after cognitive behavior therapy; 13 comparison children participated a second time after a comparable interval. Results: In the pretreatment group, the error-related negativity was reliably larger in pediatric patients with OCD in relation to comparison subjects. This difference was also evident after treatment. There was no relationship between error-related negativity and symptom severity or changes in symptom severity. Conclusions: Consistent with studies in adult patients, increased error-related brain activity is evident in pediatric patients with OCD. Furthermore, increased error-related brain activity does not appear to change as a function of symptom reduction after therapy. These results suggest that an increased error-related negativity may be a trait-like marker for psychopathology and might be a useful endophenotype.
Long-term nitroglycerin treatment: effect on direct and endothelium-mediated large coronary artery dilation in conscious dogs.
Authors: D J Stewart, J Holtz, E Bassenge
Journal: Circulation (1987)

We examined the effect of nitroglycerin (GTN) tolerance on an important determinant of nitrate-antianginal action, large coronary artery dilation, in 11 chronically instrumented conscious dogs. In addition, endothelium-mediated coronary artery dilation was studied because this shares a common dilator pathway with the nitrates, i.e., activation of soluble guanylate cyclase. With long-term GTN (1.5 micrograms/kg/min iv for 5 days) the diameters of the left circumflex and anterior descending coronary arteries showed an initial increase of 8.2 +/- 0.3% and 10.8 +/- 0.9%, respectively, returning to control levels by the second to third day of treatment. On days 4 and 5, the dose-response relations for GTN-induced epicardial artery dilation were shifted (p less than .01) to 17- to 20-fold higher doses. However, there was no attenuation of epicardial artery dilation induced by SIN-1 (n = 7), another activator of guanylate cyclase, or of endothelium-mediated dilation assessed both as flow-dependent dilation (n = 7) and as direct intra-arterial acetylcholine-induced dilation (n = 4). In addition, there was no clear tolerance to the peripheral vascular actions of GTN responsible for reflex tachycardia and increased coronary flow. We conclude that a moderate degree of nitrate tolerance to epicardial artery dilation does not affect the responsiveness to other exogenous or endogenous activators of guanylate cyclase. However, this tolerance to epicardial artery dilation, together with the maintenance of peripheral vascular actions that can induce reflex tachycardia, result in a potentially unfavorable balance of GTN effects.
Mephentermine Psychosis: Misuse of the Wyamine Inhaler
Authors: B. M. ANGRIST, J. W. SCHWEITZER, S. GERSHON, A. J. FRIEDHOFF
Journal: American Journal of Psychiatry (1970)

The authors present case reports of three patients with similar pathology in their social, vocational, and sexual adjustment who developed paranoid or paranoid hallucinatory syndromes in conjunction with the abuse of mephentermine from Wyamine inhalers. Their symptomatology appeared clinically identical to amphetamine psychosis or acute paranoid schizophrenia. The authors conclude that, if abused, the Wyamine inhaler is potentially dangerous and that its availability on the market constitutes a loophole in the current regulations governing stimulant drugs.
Enhanced Expression of the CD71 Mesangial IgA1 Receptor in Berger Disease and Henoch-Schönlein Nephritis
Authors: Elie Haddad, Ivan C. Moura, Michelle Arcos-Fajardo, Marie-Alice Macher, Veronique Baudouin, Corinne Alberti, Chantal Loirat, Renato C. Monteiro, Michel Peuchmaur
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. IgA nephropathy (IgA-N) that comprises Berger disease and Henoch-Schönlein Purpura (HSP) nephritis is defined by mesangial IgA deposits. Recently, this group has characterized a new receptor for IgA, the transferrin receptor (CD71), expressed on mesangial cells. To assess whether CD71 was involved in the pathogenesis of IgA-N, its expression was analyzed together with IgA deposits on 16 kidney biopsies from 16 patients with Berger disease (n = 4) or HSP (n = 12). These biopsies were compared with 17 kidney biopsies of a group of 15 patients (control group) with other glomerulonephritis, including systemic lupus erythematosus, poststreptococcal acute glomerulonephritis, membranoproliferative glomerulonephritis, steroid-sensitive minimal change nephrotic syndrome, steroid-resistant idiopathic nephrotic syndrome with focal and segmental glomerulosclerosis, and persistent and isolated proteinuria with minimal change on kidney biopsy. In this control group, IgA deposits could be observed in eight kidney biopsies of seven patients. These biopsies were also compared with normal kidney specimens (normal group). In normal kidney, it was found that CD71 was linearly expressed on tubular epithelium but was either not expressed or very dimly in glomeruli. In contrast, CD71 was strongly expressed in 105 of the 107 glomeruli of the kidney biopsies from the IgA-N group. For the control group, it was found that expression of CD71 in glomeruli was correlated to the presence of IgA deposits. Indeed, among the 87 glomeruli of nine kidney biopsies (eight patients) without IgA fixation, 78 exhibited no CD71 expression and nine exhibited a very dim one. On the other hand, all 49 glomeruli of the eight kidney biopsies (seven patients) in which IgA deposits were detected exhibited CD71 expression (P < 10(-4)). Performance of dual-labeling studies with confocal microscopy on kidney biopsies of IgA-N patients demonstrated that most of the IgA deposits co-localized with CD71. It was also demonstrated that the intensity of the expression of CD71 was not linked to the intensity of clinical or biologic findings but to the intensity of cellular proliferation in both IgA-N and control groups. These results show that mesangial CD71 expression is not specific to IgA-N. However, the association between IgA deposits and CD71 expression and their co-localization in the mesangium provide strong evidence that CD71 is a major IgA receptor on mesangial cells.