tbuckley/cabot-search huggingface dataset:
Tumor Thymidylate Synthase 1494del6 Genotype As a Prognostic Factor in Colorectal Cancer Patients Receiving Fluorouracil-Based Adjuvant Treatment
Authors: Emma Dotor, Miriam Cuatrecases, María Martínez-Iniesta, Matilde Navarro, Felip Vilardell, Elisabeth Guinó, Laura Pareja, Agnés Figueras, David G. Molleví, Teresa Serrano, Javier de Oca, Miguel A. Peinado, Víctor Moreno, Josep Ramón Germà, Gabriel Capellá, Alberto Villanueva
Journal: Journal of Clinical Oncology (2006)

The purpose of this study was to analyze the value of germline and tumor thymidylate synthase (TS) genotyping as a prognostic marker in a series of colorectal cancer patients receiving adjuvant fluorouracil (FU) -based treatment.One hundred twenty-nine colorectal cancer patients homogeneously treated with FU plus levamisole or leucovorin in the adjuvant setting were included. TS enhancer region, 3R G > C single nucleotide polymorphism (SNP), and TS 1494del6 polymorphisms were assessed in both fresh-frozen normal mucosa and tumor. Mutational analyses of TS and allelic imbalances were studied in all primary tumors and in 18 additional metachronic metastases. TS protein immunostaining was assessed in an expanded series of 214 tumors. Multivariate Cox models were adjusted for stage, differentiation, and location.Tumor genotyping (frequency of allelic loss, 26%) showed that the 3R/3R genotype was associated with a better outcome (hazard ratio [HR] = 0.38; 95% CI, 0.16 to 0.93; P = .020 for the recessive model). 3R G > C SNP genotyping did not add prognostic information. Tumor TS 1494del6 allele (frequency of allelic loss, 36%) was protective (for each allele with the deletion, based on an additive model, HR = 0.42; 95% CI, 0.22 to 0.82; P = .0034). Both polymorphisms were in strong linkage disequilibrium (D' = 0.71, P < .001), and the 3R/-6 base pair (bp) haplotype showed a significant overall survival benefit compared with the most prevalent haplotype 2R/+6bp (HR = 0.42; 95% CI, 0.20 to 0.85; P = .017). No TS point mutation was detected in primary tumors or metastases. TS protein immunostaining was not associated with survival or any of the genotypes analyzed.Tumor TS 1494del6 genotype may be a prognostic factor in FU-based adjuvant treatment of colorectal cancer patients.
Messenger Molecules and Cell Death
Authors: Thomas W. Sedlak, Solomon H. Snyder
Journal: JAMA (2006)

Programmed cell death, also called apoptosis, participates not only in normal physiologic processes such as development of the immune system, but also in many diseases. A loss of normal cell death may occur in cancer, and excessive cell death is found in a variety of neurodegenerative conditions. We describe 3 distinct pathways that regulate cell death. First, bilirubin, often thought to be a toxic end product of heme metabolism, serves as a physiologic cytoprotectant that may attenuate multiple forms of morbidity. In a second pathway, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mediates a novel cell death cascade. Cytotoxic stimuli, via nitric oxide generation, lead to the binding of GAPDH to the protein Siah1, translocation of GAPDH-Siah1 to the nucleus, and ultimately cell death. Third, cytochrome c, released from mitochondria early in apoptosis, synergizes with inositol-1,4,5-triphosphate (IP3) to elicit massive cellular calcium release, resulting in cell death. These pathways may regulate cell survival in a variety of pathologic states and represent fertile targets for novel therapies.
Untreated Initial Psychosis: Relation to Cognitive Deficits and Brain Morphology in First-Episode Schizophrenia
Authors: Beng-Choon Ho, Daniel Alicata, Julianna Ward, David J. Moser, Daniel S. O’Leary, Stephan Arndt, Nancy C. Andreasen
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Studies of patients experiencing their first episode of psychosis have demonstrated that they typically remain undiagnosed and untreated for 1–2 years. It has been postulated that prolonged untreated psychosis may have serious effects: poor response to neuroleptic medications, poor clinical outcomes, and direct neurotoxicity. This study investigated the relationships between duration of untreated initial psychosis and neurocognitive functioning and high-resolution imaging brain measurements. METHOD: A total of 156 subjects with DSM-IV schizophrenia, schizophreniform disorder, or schizoaffective disorder were evaluated during their first episode of psychosis. Measurements included nine domains of neurocognitive functioning, volumetric measures of total brain tissue, gray and white matter, and CSF, and measures of brain surface anatomy. RESULTS: The mean duration of untreated initial psychosis was 74.3 weeks. Correlations between neurocognitive functioning, brain volumetric measurements, and surface anatomy measurements with duration of untreated initial psychosis were weak; none reached statistical significance. When the group was divided on the basis of median duration of untreated initial psychosis, there were again no significant differences between the groups with long and short duration of untreated initial psychosis except on two measures (verbal memory and cortical sulcal depth). CONCLUSIONS: The absence of strong correlations suggests that untreated initial psychosis has no direct toxic neural effects. These results suggest that large-scale initiatives designed to prevent neural injury through early intervention in the prepsychotic or early psychosis phase may be based on incorrect assumptions that neurotoxicity or cognitive deterioration may be avoided. Nevertheless, early treatment is justified because it reduces suffering.
Insights from three-dimensional echocardiography: design of a new surgical approach for ventricular remodeling to relieve ischemic mitral regurgitation
Authors: N. Liel-Cohen, J.L. Guerrero, Y. Otsuji, M.D. Handschumacher, P. Hunziker, H. Tanabe, M. Scherrer-Crosbie, S. Sullivan, R.A. Levine
Journal: Journal of the American College of Cardiology (1998)
Submaximal exercise testing in the assessment of interstitial lung disease secondary to systemic sclerosis: reproducibility and correlations of the 6-min walk test
Authors: M H Buch, C P Denton, D E Furst, L Guillevin, L J Rubin, A U Wells, M Matucci-Cerinic, G Riemekasten, P Emery, H Chadha-Boreham, P Charef, S Roux, C M Black, J R Seibold
Journal: Annals of the Rheumatic Diseases (2006)

The 6-min walk test (6MWT) is increasingly used as an outcome measure in interstitial lung disease (ILD).
Randomized study of a short course of weekly cisplatin with or without amifostine in advanced head and neck cancer
Authors: A.S.T. Planting, G. Catimel, P.H.M. de Mulder, A. de Graeff, F. Höppener, I. Verweij, W. Oster, J.B. Vermorken
Journal: Annals of Oncology (1999)
Human Cardiovascular and Metabolic Response to Acute, Severe Isovolemic Anemia
Authors: Richard B. Weiskopf
Journal: JAMA (1998)

Context.—Although concern over the risks of red blood cell transfusion has resulted in several practice guidelines for transfusion, lack of data regarding the physiological effects of anemia in humans has caused uncertainty regarding the blood hemoglobin (Hb) concentration requiring treatment.Objective.—To test the hypothesis that acute isovolemic reduction of blood Hb concentration to 50 g/L in healthy resting humans would produce inadequate cardiovascular compensation and result in tissue hypoxia secondary to inadequate oxygen transport.Design.—Before and after interventional study.Setting.—Academic tertiary care medical center.Participants.—Conscious healthy patients (n=11) prior to anesthesia and surgery and volunteers not undergoing surgery (n=21).Interventions.—Aliquots of blood (450-900 mL) were removed to reduce blood Hb concentration from 131 (2) g/L to 50 (1) g/L [mean (SE)]. Isovolemia was maintained with 5% human albumin and/or autologous plasma. Cardiovascular parameters, arterial and mixed venous oxygen content, oxyhemoglobin saturation, and arterial blood lactate were measured before and after removal of each aliquot of blood. Electrocardiogram and, in a subset, Holter monitor were monitored continuously.Main Outcome Measures.—"Critical" oxygen delivery (TO2) as assessed by oxygen consumption (O2), plasma lactate concentration, and ST changes on electrocardiogram.Results.—Acute, isovolemic reduction of Hb concentration decreased systemic vascular resistance and TO2 and increased heart rate, stroke volume, and cardiac index (each P&lt;.001). We did not find evidence of inadequate oxygenation: O2 increased slightly from a mean (SD) of 3.07 (0.44) mL of oxygen per kilogram per minute (mL O2·kg−1·min−1) to 3.42 (0.54) Ml O2·kg−1·min−1 (P&lt;.001) and plasma lactate concentration did not change (0.81 [0.11] mmol/L to 0.62 [0.19] mmol/L;P=.09). Two subjects developed significant ST changes on Holter monitor: one apparently related to body position or activity, the other to an increase in heart rate (at an Hb concentration of 46-53 g/L); both occurred in young women and resolved without sequelae.Conclusions.—Acute isovolemic reduction of blood Hb concentration to 50 g/L in conscious healthy resting humans does not produce evidence of inadequate systemic TO2, as assessed by lack of change of O2 and plasma lactate concentration. Analysis of Holter readings suggests that at this Hb concentration in this resting healthy population, myocardial ischemia would occur infrequently.
Importance of Monocyte Chemoattractant Protein-1 Pathway in Neointimal Hyperplasia After Periarterial Injury in Mice and Monkeys
Authors: Kensuke Egashira, Qingwei Zhao, Chu Kataoka, Kishou Ohtani, Makoto Usui, Israel F. Charo, Ken-ichi Nishida, Shujiro Inoue, Makoto Katoh, Toshihiro Ichiki, Akira Takeshita
Journal: Circulation Research (2002)

Neointimal hyperplasia is a major cause of restenosis after coronary intervention. Because vascular injury is now recognized to involve an inflammatory response, monocyte chemoattractant protein-1 (MCP-1) might be involved in underlying mechanisms of restenosis. In the present study, we demonstrate the important role of MCP-1 in neointimal hyperplasia after cuff-induced arterial injury. In the first set of experiments, placement of a nonconstricting cuff around the femoral artery of intact mice and monkeys resulted in inflammation in the early stages and subsequent neointimal hyperplasia at the late stages. We transfected with an N-terminal deletion mutant of the human MCP-1 gene into skeletal muscles to block MCP-1 activity in vivo. This mutant MCP-1 works as a dominant-negative inhibitor of MCP-1. This strategy inhibited early vascular inflammation (monocyte infiltration, increased expression of MCP-1, and inflammatory cytokines) and late neointimal hyperplasia. In the second set of experiments, the cuff-induced neointimal hyperplasia was found to be less in CCR2-deficient mice than in control CCR2 +/+ mice. The MCP-1/CCR2 pathway plays a central role in the pathogenesis of neointimal hyperplasia in cuffed femoral artery of mice and monkeys. Therefore, the MCP-1/CCR2 pathway can be a therapeutic target for human restenosis after coronary intervention.
Identifying Large-Scale Brain Networks in Fragile X Syndrome
Authors: Scott S. Hall, Heidi Jiang, Allan L. Reiss, Michael D. Greicius
Journal: JAMA Psychiatry (2013)

<h3>Importance</h3> Fragile X syndrome (FXS) is an X-linked neurogenetic disorder characterized by a cognitive and behavioral phenotype resembling features of autism spectrum disorder. Until now, research has focused largely on identifying regional differences in brain structure and function between individuals with FXS and various control groups. Very little is known about the large-scale brain networks that may underlie the cognitive and behavioral symptoms of FXS. <h3>Objective</h3> To identify large-scale, resting-state networks in FXS that differ from control individuals matched on age, IQ, and severity of behavioral and cognitive symptoms. <h3>Design, Setting, and Participants</h3> Cross-sectional, in vivo neuroimaging study conducted in an academic medical center. Participants (aged 10-23 years) included 17 males and females with FXS and 16 males and females serving as controls. <h3>Main Outcomes and Measures</h3> Univariate voxel-based morphometric analyses, fractional amplitude of low-frequency fluctuations (fALFF) analysis, and group-independent component analysis with dual regression. <h3>Results</h3> Patients with FXS showed decreased functional connectivity in the salience, precuneus, left executive control, language, and visuospatial networks compared with controls. Decreased fALFF in the bilateral insular, precuneus, and anterior cingulate cortices also was found in patients with FXS compared with control participants. Furthermore, fALFF in the left insular cortex was significantly positively correlated with IQ in patients with FXS. Decreased gray matter density, resting-state connectivity, and fALFF converged in the left insular cortex in patients with FXS. <h3>Conclusions and Relevance</h3> Fragile X syndrome results in widespread reductions in functional connectivity across multiple cognitive and affective brain networks. Converging structural and functional abnormalities in the left insular cortex, a region also implicated in individuals diagnosed with autism spectrum disorder, suggests that insula integrity and connectivity may be compromised in FXS. This method could prove useful in establishing an imaging biomarker for FXS.
Assessment in Long-Term Care
Authors: R. L. Kane, R. A. Kane
Journal: Annual Review of Public Health (2000)

▪ Abstract Long-term care has begun to rely heavily on assessment as a basis for determining eligibility and payment for services, as well as for planning needed care. Mandated assessments have been introduced into nursing homes and will soon be required for home health care and rehabilitation. Many states use a formal structured assessment process to establish clients' eligibility for institutional or community-based care. The common feature of such assessment is attention to physical functioning, but other domains are also relevant, including affect, social function, cognition, pain and discomfort, and satisfaction. Taken together, this cluster is often referred to as quality of life. While some measures attempt to infer this information from clients' behavior, it is best obtained directly from clients' responses whenever possible. The other major component of a long term care assessment relates to obtaining information on clients' preferences and values. These data are important both for weighting the individual components of an assessment and for directly addressing preferences about the care and lifestyle available.
CASE OF PURPURA ANNULARIS TELANGIECTODES.
Authors: S. E. DORE
Journal: British Journal of Dermatology (1925)

Journal Article CASE OF PURPURA ANNULARIS TELANGIECTODES. Get access S. E. DORE, M.D., F.R.C.P. S. E. DORE, M.D., F.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 6, 1 June 1925, Pages 263–266, https://doi.org/10.1111/j.1365-2133.1925.tb09957.x Published: 01 June 1925
Ubiquitin C-terminal hydrolase 1: A novel functional marker for liver myofibroblasts and a therapeutic target in chronic liver disease
Authors: Caroline L. Wilson, Lindsay B. Murphy, Jack Leslie, Stuart Kendrick, Jeremy French, Christopher R. Fox, Neil S. Sheerin, Andrew Fisher, John H. Robinson, Dina G. Tiniakos, Douglas A. Gray, Fiona Oakley, Derek A. Mann
Journal: Journal of Hepatology (2015)
Stratification of Breast Cancer Risk in Women With Atypia: A Mayo Cohort Study
Authors: Amy C. Degnim, Daniel W. Visscher, Hal K. Berman, Marlene H. Frost, Thomas A. Sellers, Robert A. Vierkant, Shaun D. Maloney, V. Shane Pankratz, Piet C. de Groen, Wilma L. Lingle, Karthik Ghosh, Lois Penheiter, Thea Tlsty, L. Joseph Melton, Carol A. Reynolds, Lynn C. Hartmann
Journal: Journal of Clinical Oncology (2007)

Purpose Atypical hyperplasia is a well-recognized risk factor for breast cancer, conveying an approximately four-fold increased risk. Data regarding long-term absolute risk and factors for risk stratification are needed. Patients and Methods Women with atypical hyperplasia in the Mayo Benign Breast Disease Cohort were identified through pathology review. Subsequent breast cancers were identified via medical records and a questionnaire. Relative risks (RRs) were estimated using standardized incidence ratios, comparing the observed number of breast cancers with those expected based on Iowa Surveillance, Epidemiology, and End Results (SEER) data. Age, histologic factors, and family history were evaluated as risk modifiers. Plots of cumulative breast cancer incidence provided estimates of risk over time. Results With mean follow-up of 13.7 years, 66 breast cancers (19.9%) occurred among 331 women with atypia. RR of breast cancer with atypia was 3.88 (95% CI, 3.00 to 4.94). Marked elevations in risk were seen with multifocal atypia (eg, three or more foci with calcifications [RR, 10.35; 95% CI, 6.13 to 16.4]). RR was higher for younger women (&lt; 45; RR, 6.76; 95% CI, 3.24 to 12.4). Risk was similar for atypical ductal and atypical lobular hyperplasia, and family history added no significant risk. Breast cancer risk remained elevated over 20 years, and the cumulative incidence approached 35% at 30 years. Conclusion Among women with atypical hyperplasia, multiple foci of atypia and the presence of histologic calcifications may indicate “very high risk” status (&gt; 50% risk at 20 years). A positive family history does not further increase risk in women with atypia.
Assessment of noninvasive markers in identifying patients at risk in the brugada syndrome: insight into risk stratification
Authors: Takanori Ikeda, Harumizu Sakurada, Koichi Sakabe, Takao Sakata, Mitsuaki Takami, Naoki Tezuka, Takeshi Nakae, Mahito Noro, Yoshihisa Enjoji, Tamotsu Tejima, Kaoru Sugi, Tetsu Yamaguchi
Journal: Journal of the American College of Cardiology (2001)
Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle.
Authors: L Vergauwen, P Hespel, E A Richter
Journal: Journal of Clinical Investigation (1994)

The role of adenosine receptors in the regulation of muscle glucose uptake by insulin and contractions was studied in isolated rat hindquarters that were perfused with a standard medium containing no insulin or a submaximal concentration of 100 microU/ml. Adenosine receptor antagonism was induced by caffeine or 8-cyclopentyl-1,3-dipropylxantine (CPDPX). Glucose uptake and transport were measured before and during 30 min of electrically induced muscle contractions. Caffeine nor CPDPX affected glucose uptake in resting hindquarters. In contrast, the contraction-induced increase in muscle glucose uptake was inhibited by 30-50% by caffeine, as well as by CPDPX, resulting in a 20-25% decrease in the absolute rate of glucose uptake during contractions, compared with control values. This inhibition was independent of the rate of perfusate flow and only occurred in hindquarters perfused with insulin added to the medium. Thus, adenosine receptor antagonism inhibited glucose uptake during simultaneous exposure to insulin and contractions only. Accordingly, caffeine inhibited 3-O-methylglucose uptake during contractions only in oxidative muscle fibers that are characterized by a high sensitivity to insulin. In conclusion, the present data demonstrate A1 receptors to regulate insulin-mediated glucose transport in contracting skeletal muscle. The findings provide evidence that stimulation of sarcolemmic adenosine receptors during contractions is involved in the synergistic stimulation of muscle glucose transport by insulin and by contractions.
Skin manifestation of agnogenic myeloid metaplasia
Authors: Gabriel Loewy, Anna Mathew, Ariel Distenfeld
Journal: American Journal of Hematology (1994)

Abstract Agnogenic myeloid metaplasia (AMN) with myelofibrosis is a clonal malignancy of the hematopoletic stem cell. The disease is characterized by increased endothelial cell and fibroblast proliferation, resulting in increased deposition of fibronectin, laminin, and collagen in the bone marrow. In advanced disease, extramedullary hematopoiesis (EMH) is invariably seen in the spleen and liver. The lymph nodes are also frequent sites of EMH, but other organs, especially the kidneys, arenals, lungs, pleura, ovaries, gastrointestinal tract, and dura, may also be involved. Skin manifestations are rare. They may present in several ways: erythematous plaques, nodules, diffuse or papular erythema, ulcers, and bullae. Histopathology of these lesions reveals cells from one or more myeloid lineage in the dermis, erythrold, or megakaryocytic series alone or in combination. In rare cases, all three cell lines are demonstrated. © 1994 Wiley‐Liss, Inc.
Reduction in Plasma Free Fatty Acid in Patients with Chronic Obstructive Pulmonary Disease
Authors: Hiroo Wada, Hajime Goto, Erika Saitoh, Ryuji Ieki, Tatsuru Okamura, Tomohiro Ota, Shin-ichi Hagiwara, Takaharu Kodaka, Yorihiro Yamamoto
Journal: American Journal of Respiratory and Critical Care Medicine (2005)
MOUSE THYMUS-INDEPENDENT AND THYMUS-DERIVED LYMPHOID CELLS
Authors: A. Matter, B. Lisowska-Bernstein, J. E. Ryser, J.-P. Lamelin, P. Vassalli
Journal: The Journal of Experimental Medicine (1972)

The ultrastructural features of B-, T-, and surface Ig(sIg)-bearing cells have been studied on cell suspensions from lymphoid organs of mice at different stages of immunization. The cells were identified by exposure to rabbit antibodies against mouse-specific lymphocyte antigens (MSLA) or brain-associated θ antigen (BAθ) for T cells, mouse-specific bone marrow-derived lymphocyte antigens (MBLA) for B cells, and mouse Ig for sIg-bearing cells. The rabbit antibodies fixed on the cell surfaces were detected by peroxidase-labeled sheep anti-rabbit Ig antibodies or by a "bridge" technique using southern bean mosaic virus or bacteriophage T4 as the final markers. In some experiments, short-lived lymphoid cells were labeled in vivo with repeated tritiated thymidine and the ultrastructural detection of their surface antigens was combined with radioautography. MBLA+ lymphoid cells showed a whole range of ultrastructural patterns. Most were small and medium-sized lymphocytes with a clear cytoplasm containing mono- and polyribosomes, but they comprised also blasts and large cells with various amounts of endoplasmic reticulum, as well as plasma cells at different stages of maturation. sIg-bearing cells appeared to be identical with MBLA+ cells, except that sIg was less easily detectable on large blasts, and only very rarely observed on plasma cells. MSLA+ and BAθ+ cells fell into three categories. One of them (T1 cells) consisted of small to medium-sized lymphocytes with a clear cytoplasm and few organelles, mostly monoribosomes. A second consisted of large cells (T2 cells) characterized by numerous polyribosomes often in a "rosette"-like pattern, occasional dark, membrane-bound granules, and a developing "filamentous network." The third, very characteristic type, (T3 cells) was represented by dark small to medium-sized lymphocytes, usually containing large amounts of closely packed ribosomes and showing a striking accumulation of filamentous network, often condensed in large areas devoid of cell organelles. This filamentous network appeared to correspond to the cytochalasin B-sensitive system of microfilaments found in other cells and considered to be one of the contractile elements of the cell. The T3 lymphocytes showed frequently vesicles suggestive of a strong pinocytic activity, and assumed a variety of shapes, including uropods. Evidence is presented that T1 lymphocytes represent "virgin" T cells, T2 "activated," and T3 "differentiated" lymphocytes.