tbuckley/cabot-search huggingface dataset:
Neutralizing and Non-neutralizing Antibodies to Bovine Thyroid-Stimulating Hormone and its Subunits
Authors: Gildon N. Beall, Inder J. Chopra, David H. Solomon, John G. Pierce, James S. Cornell
Journal: Journal of Clinical Investigation (1973)

To test the possibility that the long-acting thyroid stimulator (LATS) might represent an immune complex either of thyroid-stimulating hormone (TSH) with anti-TSH or of a subunit of TSH with an appropriate antibody, we immunized rabbits with bovine TSH (bTSH), bLH (luteinizing hormone), and their alpha and beta subunits (bTSHalpha and bTSHbeta). Binding, neutralizing, and nonneutralizing antibodies were demonstrated in the antisera obtained. First, antisera to TSH, TSHbeta, and TSHalpha all bound [(125)I]TSH and [(125)I]TSHbeta. Anti-bTSHbeta antisera bound [(125)I]bTSHbeta better than did anti-TSH sera, while the binding of [(125)I]bTSH was similar with both types of antiserum. Second, the thyroid-stimulating activity (McKenzie bioassay) of TSH could be neutralized by incubation with various dilutions of anti-TSH or anti-TSHbeta. Finally, when incubation mixtures containing TSH and dilutions of anti-TSHbeta antisera that only partially neutralized TSH were treated with an antiserum against rabbit immunoglobulins to precipitate immune complexes, the bioassay response of the TSH was abolished. This phenomenon was not observed when antiserum to the intact hormone was substituted in the incubation mixture. The removal of TSH biological activity from a mixture of TSH and anti-bTSHbeta by addition of an anti-immunoglobulin indicated that biologically active immune complexes were formed between TSH and anti-TSHbeta but not between TSH and anti-TSH. The time-course of the bioactivity and several other characteristics of these complexes differentiate them from LATS.
Multiple alpha-globin genes in crab-eating macaques (Macaca fascicularis).
Authors: A Takenaka, S Ueda, K Terao, O Takenaka
Journal: Molecular Biology and Evolution (1991)

Alpha-globin genes in crab-eating macaques were found to be triplicated at high frequencies according to restriction-enzyme comparisons. The frequencies of triplicated alpha-globin genes in macaques originally from Malaysia and Indonesia were 0.432 and 0.275, respectively, while no triplication was found in individuals from either the Philippines or northern and central Thailand. Quadruplicated alpha-globin genes were also observed, at frequencies of 0.045 (Malaysia), 0.075 (Indonesia), and 0.021 (the Philippines). A single locus was detected in only one of 40 chromosomes from Indonesia (frequency 0.025).
PROTEST ADDRESSED TO THE PRESIDENT AND COUNCIL OF THE ROYAL COLLEGE OF SURGEONS BY THE SURGEONS OF CHELTENHAM.
Authors: None Allardyce, None Gibney, None Cannon, None Colledge, None Wollaston, None Eves, None Rumsey, None Elcum, None Winterbotham, Henry Bird, WM. Dalton, Andrew Spittall
Journal: The Lancet (1860)
Natural History of Paclitaxel-Associated Acute Pain Syndrome: Prospective Cohort Study NCCTG N08C1
Authors: Charles L. Loprinzi, Brandi N. Reeves, Shaker R. Dakhil, Jeff A. Sloan, Sherry L. Wolf, Kelli N. Burger, Arif Kamal, Nguyet A. Le-Lindqwister, Gamini S. Soori, Anthony J. Jaslowski, Paul J. Novotny, Daniel H. Lachance
Journal: Journal of Clinical Oncology (2011)

Purpose The characteristics and natural history of the paclitaxel–acute pain syndrome (P-APS) and paclitaxel's more chronic neuropathy have not been well delineated. Methods Patients receiving weekly paclitaxel (70 to 90 mg/m 2 ) completed daily questionnaires and weekly European Organisation for Research and Treatment of Cancer (EORTC) Chemotherapy-Induced Peripheral Neuropathy (CIPN) –20 instruments during the entire course of therapy. Results P-APS symptoms peaked 3 days after chemotherapy. Twenty percent of patients had pain scores of 5 to 10 of 10 with the first dose of paclitaxel. Sensory neuropathy symptoms were more prominent than were motor or autonomic neuropathy symptoms. Of the sensory neuropathy symptoms, numbness and tingling were more prominent than was shooting or burning pain. Patients with higher P-APS pain scores with the first dose of paclitaxel appeared to have more chronic neuropathy. Conclusion These data support that the P-APS is related to nerve pathology as opposed to being arthralgias and/or myalgias. Numbness and tingling are more prominent chronic neuropathic symptoms than is shooting or burning pain.
PC3 Human Prostate Carcinoma Cell Holoclones Contain Self-renewing Tumor-Initiating Cells
Authors: Hangwen Li, Xin Chen, Tammy Calhoun-Davis, Kent Claypool, Dean G. Tang
Journal: Cancer Research (2008)

Primary keratinocytes exhibit three typical clonal morphologies represented by holoclones, meroclones, and paraclones, with holoclones containing self-renewing stem cells, and meroclones and paraclones containing more mature and differentiated cells. Interestingly, long-term-cultured human epithelial cancer cells in clonal cultures also form holoclones, meroclones, and paraclones, and tumor cell holoclones have been hypothesized to harbor stem-like cells or cancer stem cells. However, the key question of whether tumor cell holoclones genuinely contain tumor-initiating cells has not been directly addressed. Here, using PC3 human prostate carcinoma cells as a model, we provide direct experimental evidence that tumor cell holoclones contain stem-like cells that can initiate serially transplantable tumors. Importantly, holoclones derived from either cultured PC3 cells or holoclone-initiated tumors can be serially passaged and regenerate all three types of clones. In contrast, meroclones and paraclones cannot be continuously propagated and fail to initiate tumor development. Phenotypic characterizations reveal high levels of CD44, alpha(2)beta(1) integrin, and beta-catenin expression in holoclones, whereas meroclones and paraclones show markedly reduced expression of these stem cell markers. The present results have important implications in understanding morphologic heterogeneities and tumorigenic hierarchies in human epithelial cancer cells.
Rhinitis and Blood Pressure in Adults
Authors: Joachim Heinrich, Rebekka Topp, Sabine Brasche
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Recently, a study of 330 adults reported increased systolic blood pressure and higher hypertension rates in men with rhinitis. We replicated this study using data from a population-based sample of 896 subjects participating in the European Respiratory Health Survey and in a study on "Monitoring of Trends and Determinants of Cardiovascular Diseases" in Erfurt, Germany. Rhinitis was assessed by questionnaire, blood pressure was measured using a standardized method, and subjects were asked about current use of any high blood pressure medication. After adjustment for age, body mass index, and smoking, neither average systolic (p = 0.17) nor diastolic blood pressure (p = 0.60) was statistically significantly different between men with and without rhinitis. The adjusted prevalence rate of hypertension was also not different between males with and without rhinitis (p = 0.25). In addition, no statistically significant associations between rhinitis and blood pressure were seen in women. We could not confirm the conclusion of the previous study that men with rhinitis need special attention for blood pressure control.
The Use of Pleurx Drains in the Management of Persistent Pleural Effusion Secondary to Malignant Mesothelioma: A 5 Year Experience
Authors: S. Bazerbashi, M. Abdelaziz, B. Ahlijha, A. Marchbank, M. Awan, J. Rahamim, M. Unswoth-White
Journal: International Journal of Surgery (2010)
Estimates of DNA and protein sequence divergence: an examination of some assumptions.
Authors: G B Golding
Journal: Molecular Biology and Evolution (1984)

Some of the assumptions underlying estimates of DNA and protein sequence divergence are examined. A solution for the variance of these estimates that allows for different mutation rates and different population sizes in each species and for an arbitrary structure in the initial population is obtained. It is shown that these conditions do not strongly affect estimates of divergence. In general, they cause the variance of divergence to be smaller than a binomial variance. Thus, the binomial variance that is usually assumed for these estimates is safely conservative. It is shown that variability in the mutation rate among sites can have an effect as large as or larger than variability in the mutation rate among bases. Variability in the mutation rate among bases and among sites causes the number of substitutions between two sequences to be underestimated. Protein and DNA sequences from several species are collected to estimate the variability in mutation rates among sites. When many homologous sequences are known, standard methods to estimate this variability can be used. The estimates of this variability show that this factor is important when considering the spectrum of spontaneous mutations and is strongly reflected in the divergence of sequences. Smaller variability is found for the third position of codons than for the first and second codon positions. This may be because of less selective constraints on this position or because the third position has been saturated with mutations for the sequences examined.
Inhibition of Incorporation of Leucine into Myocardial Proteins of the Rat by Antiarrhythmic Agents
Authors: Barry M. Beller, Stephen Mongillo
Journal: Circulation Research (1969)

Incorporation of tritiated leucine into myocardial proteins was inhibited at low concentration by quinidine, procaine amide, and diphenylhydantoin, but not by lidocaine or propranolol. This inhibition could be demonstrated in vitro and when the animals were treated with these agents. The relationship between this finding and myocardial depression produced by these antiarrhythmic agents is not known but may reside in general depression of cellular metabolism and protein synthesis or in inhibition of synthesis of a specific membrane carrier protein.
Preclinical Assessment of Efficacy of Radiation Dose Painting Based on Intratumoral FDG-PET Uptake
Authors: Daniela Trani, Ala Yaromina, Ludwig Dubois, Marlies Granzier, Sarah G.J.A. Peeters, Rianne Biemans, Georgi Nalbantov, Natasja Lieuwes, Brigitte Reniers, Esther E.G.C. Troost, Frank Verhaegen, Philippe Lambin
Journal: Clinical Cancer Research (2015)

Abstract Purpose: We tested therapeutic efficacy of two dose painting strategies of applying higher radiation dose to tumor subvolumes with high FDG uptake (biologic target volume, BTV): dose escalation and dose redistribution. We also investigated whether tumor response was determined by the highest dose in BTV or the lowest dose in gross tumor volume (GTV). Experimental Design: FDG uptake was evaluated in rat rhabdomyosarcomas prior to irradiation. BTV was defined as 30% of GTV with the highest (BTVhot) or lowest (BTVcold) uptake. To test efficacy of dose escalation, tumor response (time to reach two times starting tumor volume, TGTV2) to Hot Boost irradiation (40% higher dose to BTVhot) was compared with Cold Boost (40% higher dose to BTVcold), while mean dose to GTV remained 12 Gy. To test efficacy of dose redistribution, TGTV2 after Hot Boost was compared with uniform irradiation with the same mean dose (8 or 12 Gy). Results: TGTV2 after 12 Gy delivered heterogeneously (Hot and Cold Boost) or uniformly were not significantly different: 20.2, 19.5, and 20.6 days, respectively. Dose redistribution (Hot Boost) with 8 Gy resulted in faster tumor regrowth as compared with uniform irradiation (13.3 vs. 17.1 days; P = 0.026). Further increase in dose gradient to 60% led to a more pronounced decrease in TGTV2 (10.9 days; P &amp;lt; 0.0001). Conclusions: Dose escalation effect was independent of FDG uptake in target tumor volume, while dose redistribution was detrimental in this tumor model for dose levels applied here. Our data are consistent with the hypothesis that tumor response depends on the minimum intratumoral dose. Clin Cancer Res; 21(24); 5511–8. ©2015 AACR.
Evaluation of psychosocial distress in patients treated in a community-based oncology group practice in Germany
Authors: U. Mergenthaler, J. Heymanns, H. Köppler, J. Thomalla, C. van Roye, J. Schenk, R. Weide
Journal: Annals of Oncology (2010)

Systematic evaluation of psychosocial distress in oncology outpatients is an important issue. We assessed feasibility and benefit of standardized routine screening using the Distress Thermometer (DT) and Problem List (PL) in all patients of our community-based hematooncology group practice.One thousand four hundred forty-six patients were screened between July 2008 and September 2008. Five hundred randomly selected patients were sent a feedback form.The average distress level was 4.7, with 37% indicating a distress level >5. Patients with nonmalignant diseases (81% autoimmune diseases or hereditary hemochromatosis) showed the highest distress level of 5.2. Most distressed were patients who just learned about relapse or metastases (6.4), patients receiving best supportive care (5.4) and patients receiving adjuvant antihormonal therapy (5.4). Ninety-seven percent of patients appreciated to speak to their doctor about their distress. Fifty-six percent felt better than usual after this consultation.DT and PL are feasible instruments to measure distress in hematooncology outpatients receiving routine care. DT and PL are able to improve doctor-patient communication and thus should be implemented in routine patient care. The study shows that distress is distributed differently between individuals, disease groups and treatment phases.
Distinguishing Second Primary Tumors From Lung Metastases in Patients With Head and Neck Sauamous Cell Carcinoma
Authors: P. P. Leong, W. M. Koch, A. Reed, D. Eisele, D. Sidransky, J. Jen, B. Rezai, D.-J. Lee, W. H. Westra
Journal: JNCI Journal of the National Cancer Institute (1998)

In patients with head and neck squamous cell carcinoma (HNSCC), a squamous cell carcinoma (SCC) in the lung represents either another primary tumor or a metastasis. This distinction greatly influences patient prognosis and could guide treatment strategies, but the nature of a solitary lung nodule is often difficult to discern by use of standard clinical and histologic parameters. Comparison of genetic alterations in the tumors could resolve this dilemma.We compared paired tumors from 16 patients with HNSCC and a solitary lung SCC for loss (i.e., deletion) of loci on chromosomal arms 3p and 9p. Losses at these loci occur early during neoplastic transformation of the respiratory tract. DNA from microdissected tumors and normal tissues was subjected to polymerase chain reaction-based microsatellite analysis. An effort was also made to distinguish primary lung cancers from lung metastases on the basis of clinical and histopathologic features.In most cases, comparison of genetic alterations clarified the relationship between the lung tumor and the primary HNSCC. The paired tumors from 10 patients had concordant patterns of loss at all loci suggesting metastatic spread, whereas three paired tumors had discordant patterns of loss at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings.In patients with HNSCC and a solitary SCC in the lung, microsatellite analysis provides a rapid genetic approach for discerning clonal relationships. In such patients, we found that a solitary SCC in the lung more likely represents a metastasis than an independent lung cancer. Microsatellite analysis could potentially be applied to any patient with multiple tumors, where tumor relationships are not clear on clinical, radiographic, or even histopathologic grounds.
KEAP1 Is a Redox Sensitive Target That Arbitrates the Opposing Radiosensitive Effects of Parthenolide in Normal and Cancer Cells
Authors: Yong Xu, Fang Fang, Sumitra Miriyala, Peter A. Crooks, Terry D. Oberley, Luksana Chaiswing, Teresa Noel, Aaron K. Holley, Yanming Zhao, Kelley K. Kiningham, Daret K. St. Clair, William H. St. Clair
Journal: Cancer Research (2013)

Elevated oxidative stress is observed more frequently in cancer cells than in normal cells. It is therefore expected that additional exposure to a low level of reactive oxygen species (ROS) will push cancer cells toward death, whereas normal cells might maintain redox homeostasis through adaptive antioxidant responses. We previously showed that parthenolide enhances ROS production in prostate cancer cells through activation of NADPH oxidase. The present study identifies KEAP1 as the downstream redox target that contributes to parthenolide's radiosensitization effect in prostate cancer cells. In vivo, parthenolide increases radiosensitivity of mouse xenograft tumors but protects normal prostate and bladder tissues against radiation-induced injury. Mechanistically, parthenolide increases the level of cellular ROS and causes oxidation of thioredoxin (TrX) in prostate cancer cells, leading to a TrX-dependent increase in a reduced state of KEAP1, which in turn leads to KEAP1-mediated PGAM5 and Bcl-xL (BCL2L1) degradation. In contrast, parthenolide increases oxidation of KEAP1 in normal prostate epithelial cells, leading to increased Nrf2 (NFE2L2) levels and subsequent Nrf2-dependent expression of antioxidant enzymes. These results reveal a novel redox-mediated modification of KEAP1 in controlling the differential effect of parthenolide on tumor and normal cell radiosensitivity. Furthermore, they show it is possible to develop a tumor-specific radiosensitizing agent with radioprotective properties in normal cells.
Lupus-specific health outcome measure for US patients: the LupusQoL-US version
Authors: M Jolly, A S Pickard, C Wilke, R A Mikolaitis, L-S Teh, K McElhone, L Fogg, J Block
Journal: Annals of the Rheumatic Diseases (2009)

Background: Patient-reported outcomes are valuable for the management of chronic diseases like systematic lupus erythematosus (SLE), but no measures have been validated for use in US-based patients with SLE. Objectives: To adapt and assess the validity and reliability of an SLE-specific quality of life (QoL) measure developed in the United Kingdom, the LupusQoL, for use in US-based patients with SLE. Methods: Debriefing interviews of subjects with SLE guided the language modifications of the tool. The LupusQoL-US, SF-36 and EQ5D were administered. Internal consistency (ICR) and test–retest (TRT) reliability, convergent and discriminative validity were examined. Factor analyses were performed. Results: The mean (SD) age of the 185 subjects with SLE was 42.5 (12.9) years. ICR and TRT of the eight domains ranged from 0.85 to 0.94 and 0.68 to 0.92, respectively. Related domains on the SF-36 correlated with the LupusQoL domains (physical health and physical function r = 0.73, physical health and role physical r = 0.57, emotional health and mental health r = 0.72, emotional health and role emotional r = 0.48, pain and bodily pain r = 0.66, fatigue and vitality r = 0.70, planning and social functioning r = 0.58). Most LupusQoL-US domains could discriminate between subjects with varied disease activity and damage. Principal component analysis disclosed five factors in the US version, with physical function, pain and planning items loading on one factor. Conclusions: These data provide evidence to support the psychometric properties of the LupusQoL-US, suggesting its utility as an assessment tool for patients with SLE in the USA.
Local regulation of blood flow in the feline jejunum. A possible role for endoluminally released substance P.
Authors: C J Yeo, B M Jaffe, M J Zinner
Journal: Journal of Clinical Investigation (1982)

Serotonin and substance P of gastrointestinal origin have been measured by radioimmunoassay in the bowel lumen under basal and stimulated conditions. To investigate the possibility that local blood flow may be influenced by these endoluminal hormones, 26 cats were studied with exogenous serotonin and substance P infused endoluminally into isolated proximal jejunal segments in vivo. Regional blood flow was measured by using the radioactive microsphere technique before, during, and after the endoluminal instillation of two doses of substance P (3.9 and 30 ng/min) or serotonin (0.9 and 21 micrograms/min). Neither dose of substance P changed systemic blood pressure. Substance P at the low dose caused an increase in blood flow to the experimental jejunal mucosa (from 53 +/- 10 ml/min per 100 g to 102 +/- 20 ml/min per 100 g, P less than 0.01). The higher dose of endoluminal substance P similarly increased blood flow to the experimental jejunal mucosal fraction, and also increased blood flow to the experimental jejunal muscularis fraction (from 17 +/- 3 ml/min per 100 g to 23 +/- 3 ml/min per 100 g, P less than 0.02). Serotonin increased blood flow to the experimental jejunal muscularis only at the high dose (17 +/- 4 ml/min per 100 g to 25 +/- 4 ml/min per 100 g tissue, P less than 0.01). These results provide evidence for a dose-related local effect of endoluminal substance P on gastrointestinal blood flow.
Reward-Based Spatial Learning in Unmedicated Adults With Obsessive-Compulsive Disorder
Authors: Rachel Marsh, Gregory Z. Tau, Zhishun Wang, Yuankai Huo, Ge Liu, Xuejun Hao, Mark G. Packard, Bradley S. Peterson, H. Blair Simpson
Journal: American Journal of Psychiatry (2014)

Objective: The authors assessed the functioning of mesolimbic and striatal areas involved in reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder (OCD). Method: Functional MRI blood-oxygen-level-dependent response was compared in 33 unmedicated adults with OCD and 33 healthy, age-matched comparison subjects during a reward-based learning task that required learning to use extramaze cues to navigate a virtual eight-arm radial maze to find hidden rewards. The groups were compared in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudorandomly to experimentally prevent learning. Results: Both groups learned to navigate the maze to find hidden rewards, but group differences in neural activity during navigation and reward processing were detected in mesolimbic and striatal areas. During navigation, the OCD group, unlike the healthy comparison group, exhibited activation in the left posterior hippocampus. Unlike healthy subjects, participants in the OCD group did not show activation in the left ventral putamen and amygdala when anticipating rewards or in the left hippocampus, amygdala, and ventral putamen when receiving unexpected rewards (control condition). Signal in these regions decreased relative to baseline during unexpected reward receipt among those in the OCD group, and the degree of activation was inversely associated with doubt/checking symptoms. Conclusions: Participants in the OCD group displayed abnormal recruitment of mesolimbic and ventral striatal circuitry during reward-based spatial learning. Whereas healthy comparison subjects exhibited activation in this circuitry in response to the violation of reward expectations, unmedicated OCD participants did not and instead over-relied on the posterior hippocampus during learning. Thus, dopaminergic innervation of reward circuitry may be altered, and future study of anterior/posterior hippocampal dysfunction in OCD is warranted.