tbuckley/cabot-search huggingface dataset:
&lt;italic&gt;Propionibacterium acnes&lt;/italic&gt;-Mediated Humoral Immune Responses to Tumor-Specific Antigens on Rat Liver Cells Transformed In Vitro by Chemical Carcinogens
Authors: T. Yokota, S. Katahira, K. Konno, K. Minami
Journal: JNCI Journal of the National Cancer Institute (1978)

Effects of Propionibacterium acnes on production of antibodies against tumor-specific membrane antigens were investigated in syngeneic inbred BD IV and BD VI rats. BD rat liver cell lines transformed in vitro by chemical carcinogens were used as target cells for tumor-specific antigens. By membrane immunofluorescence, antibodies against these rat liver cell lines were detected in syngeneic BD rat sera. Antibodies were produced in syngeneic rats under the adjuvant effect of heat-killed P. acnes only. In assays with various target cells and absorption experiments, the antibodies reacted with a tumor-specific individual antigen or tumor-specific cross-reacting antigen on the surfaces of transformed BD rat liver cells. No antibodies against these antigens were found in the sera obtained from syngeneic rats immunized with either the transformed cell lines or P. acnes but not with both. Freund's complete adjuvant did not induce antibodies against these tumor-specific antigens.
Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT–YB1–MDR1 Signaling Pathway
Authors: Dongliang Mo, Hongbo Fang, Kaifeng Niu, Jing Liu, Meng Wu, Shiyou Li, Tienian Zhu, Mohammed A. Aleskandarany, Arvind Arora, Dileep N. Lobo, Srinivasan Madhusudan, Adayabalam S. Balajee, Zhenfen Chi, Yongliang Zhao
Journal: Cancer Research (2016)

Elevation of the DNA-unwinding helicase RECQL4, which participates in various DNA repair pathways, has been suggested to contribute to the pathogenicity of various human cancers, including gastric cancer. In this study, we addressed the prognostic and chemotherapeutic significance of RECQL4 in human gastric cancer, which has yet to be determined. We observed significant increases in RECQL4 mRNA or protein in >70% of three independent sets of human gastric cancer specimens examined, relative to normal gastric tissues. Strikingly, high RECQL4 expression in primary tumors correlated well with poor survival and gastric cancer lines with high RECQL4 expression displayed increased resistance to cisplatin treatment. Mechanistic investigations revealed a novel role for RECQL4 in transcriptional regulation of the multidrug resistance gene MDR1, through a physical interaction with the transcription factor YB1. Notably, ectopic expression of RECQL4 in cisplatin-sensitive gastric cancer cells with low endogenous RECQL4 was sufficient to render them resistant to cisplatin, in a manner associated with YB1 elevation and MDR1 activation. Conversely, RECQL4 silencing in cisplatin-resistant gastric cancer cells with high endogenous RECQL4 suppressed YB1 phosphorylation, reduced MDR1 expression, and resensitized cells to cisplatin. In establishing RECQL4 as a critical mediator of cisplatin resistance in gastric cancer cells, our findings provide a therapeutic rationale to target RECQL4 or the downstream AKT-YB1-MDR1 axis to improve gastric cancer treatment. Cancer Res; 76(10); 3057-66. ©2016 AACR.
Phase II trial of BB-10901 (huN901-DM1) given weekly for four consecutive weeks every 6 weeks in patients with relapsed SCLC and CD56-positive small cell carcinoma
Authors: F. Fossella, J. McCann, A. Tolcher, H. Xie, L.-L. Hwang, C. Carr, K. Berg, R. Fram
Journal: Journal of Clinical Oncology (2005)

7159 Background: BB-10901 is an immunoconjugate created by conjugation of the cytotoxic maytansinoid drug DM1 to a humanized version of the murine monoclonal antibody N901. BB-10901 binds with high affinity to CD56. The latter is expressed on a variety of solid tumors including small cell lung carcinoma. Methods: A phase I dose escalating study was conducted in patients with small cell lung carcinoma and other CD56-positive solid tumors. The maximum tolerated dose was defined as 60 mg/m2/week given as an IV infusion for four consecutive weeks every six weeks. A phase II extension of this trial is underway in which patients with relapsed small cell lung carcinoma or with relapsed CD56+ non-pulmonary small cell carcinoma are treated on this regimen. The Phase II extension consists of two stages. 14 patients are initially enrolled. The study is expanded to 35 patients if an objective response is observed among the initial 14 patients. Results: 10 patients have been treated on the Phase II extension of the study. One patient had a serious adverse event consisting of aseptic meningitis. Symptoms resolved within one week. No other drug related SAEs have occurred among the ten patients. Preliminary evaluation reveals no evidence of cardiac, thyroid, or adrenal dysfunction secondary to BB-10901. Initial pharmacokinetic findings demonstrate an increase in both t½ (terminal half life) and AUC (Area Under Curve) in Week 2 compared to Week 1 in two patients whose data are available. The t½ increased from 8.4 to 11.2 hours (h) and from 9.2 to 14.3 h from Week 1 to Week 2, respectively in the two patients. Evidence of clinical activity was noted in three patients. A patient with relapsed small cell lung carcinoma has preliminary evidence of a partial response. A patient with relapsed small cell carcinoma had a non-sustained partial response. A third patient with relapsed SCLC had a minor response. Conclusions: The study provides evidence of safety and clinical activity of BB-10901. The prolongation in t½ that occurred after initial dosing is consistent with saturation of CD56 positive sites such as NK cells. The study will be expanded to 35 patients upon confirmation of the partial response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImmunoGen ImmunoGen
Bone loss, pain and inflammation: three faces of ACPA in RA pathogenesis
Authors: Jeremy Sokolove, David Pisetsky
Journal: Annals of the Rheumatic Diseases (2016)

In two papers, investigators from the Karolinska Institutet provide an exciting new perspective on the role of antibodies to citrullinated proteins (anticitrullinated protein antibodies or ACPA) in the pathogenesis of rheumatoid arthritis (RA).1 ,2 The data are intriguing and they point to unexpected mechanisms by which these autoantibodies may drive disease manifestations. By revealing a potential role of ACPA in the bone loss and pain that are cardinal features of RA, the investigative teams have advanced a new concept that may (same comment) account for the signs and symptoms of RA at the onset of synovitis as well as during the period of the most intense activity.

The first study by Krishnamurthy et al 1 addressed the basis of RA bone loss. Building on prior research on effects of ACPA on bone,3 the study demonstrates that polyclonal ACPA derived from patients with RA as well as select monoclonal ACPA can induce osteoclastogensis in human monocytes in vitro. This process appears dependent on a combination of intracellular protein citrullination in the osteoclast as well as autocrine production of (interleukin 8) IL-8. Furthermore, in an animal model, the investigators show that intravenous administration of monoclonal ACPA can induce trabecular bone loss as measured by micro computed tomography (microCT). In this model, the administration of ACPA did not induce synovial inflammation, with the inhibition of bone loss by IL-8 blockade but not by tumour necrosis factor (TNF) blockade suggesting a mechanism for bone loss beyond inflammation.1

The second study by Wigerblad et al 2 used similar reagents to explore the effects of ACPA on pain. As the results of the study show, the administration of either polyclonal human ACPA or murinised monoclonal ACPA derived from human RA synovium can induce both spontaneous and evoked pain behaviour in mice. This …
Tc-99m MDP Uptake by Adrenal Metastases From Nonsmall Cell Carcinoma of the Lung
Authors: Tamer ??z??lker, Filiz ??z??lker, Tevfik ??zpa??ac, Sadk Erg??r, Mehmet M??lazmo??lu
Journal: Clinical Nuclear Medicine (2005)

In a 51-year-old male patient with nonsmall cell lung cancer (NSCLC), masses were detected with ultrasonography and computed tomography in both adrenal glands. The results of fine needle aspiration biopsies from both adrenal glands diagnosed metastases from lung cancer. Whole-body bone scan of the patient revealed metastatic lesions in the left hemipelvis and left femur together with Tc-99m MDP uptake in both adrenal gland metastases.
Preschool children's erroneous allegations of sexual molestation
Authors: A Yates, T Musty
Journal: American Journal of Psychiatry (1988)

Occasionally, a preschool child may erroneously accuse a parent of molestation. When this occurs, the child usually believes that his or her story is correct. A false accusation can be made when an adult has persuaded a child that the sexual events actually occurred, when a child in the oedipal stage has misinterpreted caregiving ministrations, when a child's thought processes are confused by primary process material, or when a child is secondarily involved in the projective identifications of a dominant caregiver. More than one of these mechanisms may operate in a given case.
Tumor-Associated Glycoprotein (TAG-72) in Ovarian Carcinomas Defined by Monoclonal Antibody 872.3
Authors: A Thor, F Gorstein, N Ohuchi, C A Szpak, W W Johnston, J Schlom
Journal: JNCI Journal of the National Cancer Institute (1986)

Murine IgG1 monoclonal antibody (MoAb) B72.3, reactive with a high molecular weight glycoprotein complex [designated tumor-associated glycoprotein-72 (TAG-72)] was shown, with the use of the avidin-biotin-complex-immunoperoxidase technique and surgically resected tissues, to be reactive with a variety of histologic tumor types. TAG-72 is expressed in at least 5% (and up to 100%) of the malignant epithelial cells in 77% (n = 52) of human primary cancers and 71% (n = 31) of metastatic ovarian cancers of the common "epithelia" histologic category. Of these, several histologic types, including serous and mucinous cystadenocarcinomas, undifferentiated carcinomas, and less common types of ovarian carcinoma, were all shown to express TAG-72. In contrast, normal ovarian tissues and 26 of 27 benign ovarian tumors of various histologic types failed to express similar levels of TAG-72. Of interest is the 1 benign tumor that demonstrated unusual glandular complexity, as well as 3 tumors designated as borderline malignancy, that contained elevated TAG-72 expression. MoAb B72.3 also was used successfully to detect ovarian carcinoma cells in 28 cytologic preparations of human serous effusions and peritoneal washings. The reactivity of MoAb B72.3 was shown to be distinct from that of MoAb OC125 and an anti-CEA MoAb B1.1. The potential applications of MoAb B72.3 in the study of human ovarian cancer cell populations, as well as in several aspects of the management of human ovarian cancer, are discussed.
Progressive ventilation inhomogeneity in infants with cystic fibrosis after pulmonary infection
Authors: Shannon J. Simpson, Sarath Ranganathan, Judy Park, Lidija Turkovic, Roy M. Robins-Browne, Billy Skoric, Kathryn A. Ramsey, Tim Rosenow, Georgia L. Banton, Luke Berry, Stephen M. Stick, Graham L. Hall
Journal: European Respiratory Journal (2015)

Measures of ventilation distribution are promising for monitoring early lung disease in cystic fibrosis (CF). This study describes the cross-sectional and longitudinal impacts of pulmonary inflammation and infection on ventilation homogeneity in infants with CF. Infants diagnosed with CF underwent multiple breath washout (MBW) testing and bronchoalveolar lavage at three time points during the first 2 years of life. Measures were obtained for 108 infants on 156 occasions. Infants with a significant pulmonary infection at the time of MBW showed increases in lung clearance index (LCI) of 0.400 units (95% CI 0.150–0.648; p=0.002). The impact was long lasting, with previous pulmonary infection leading to increased ventilation inhomogeneity over time compared to those who remained free of infection (p&lt;0.05). Infection with Haemophilus influenzae was particularly detrimental to the longitudinal lung function in young children with CF where LCI was increased by 1.069 units for each year of life (95% CI 0.484–1.612; p&lt;0.001). Pulmonary infection during the first year of life is detrimental to later lung function. Therefore, strategies aimed at prevention, surveillance and eradication of pulmonary pathogens are paramount to preserve lung function in infants with CF.
The Psychiatric Status Schedule for Asian Americans
Authors: J Yamamoto, J Lam, W I Choi, S Reece, S Lo, D S Hahn, L Fairbanks
Journal: American Journal of Psychiatry (1982)

Because Asian Americans who need to be diagnosed often do not speak English, the authors translated the Psychiatric Status Schedule into several Asian languages and devised an audiovisual version of the schedule. They tested the validity of the audiovisual version by comparing the computer diagnoses derived from interviews by mental health professionals who used the standard translated version with the computer diagnoses of mental health professionals and volunteers who used the audiovisual version. Sixty subjects were diagnosed: 20 Chinese-speaking patients, 20 Korean-speaking patients, and 20 Japanese-speaking subjects. Moderate reliability was found between those who used the standard translated version and those who used the audiovisual version.
Clinical trials of agents that reverse multidrug-resistance.
Authors: M M Gottesman, I Pastan
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.4.409 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2564427 Clinical trials of agents that reverse multidrug-resistance. M M GottesmanxM M GottesmanSearch for articles by this author , I PastanxI PastanSearch for articles by this author Show More National Cancer Institute Bethesda, MD. https://doi.org/10.1200/JCO.1989.7.4.409 First Page PDF © 1989 by American Society of Clinical Oncology
Adenocarcinoma and Proliferative Hyperplasia of the Prostate Gland in Female Rattus (Mastomys) Natalensis
Authors: Katharine C. Snell, Harold L. Stewart
Journal: JNCI Journal of the National Cancer Institute (1965)

This is a report of adenocarcinoma of the prostate gland in one Mastomys and proliferative hyperplasia in 4 others among a group of 55 untreated virgin females.
Abstract 16912: Molecular Mechanisms Underlying the Beneficial Effects of Inhibition of Soluble Epoxide Hydrolase in the Prevention of Atrial Fibrillation
Authors: Padmini Sirish, Ning Li, Valeriy Timofeyev, Xiao-Dong Zhang, Lianguo Wang, Jun Yang, Kin Sing Lee, Ahmed Bettaieb, Victor Lau, Javier Lopez, Fawaz Haj, Crystal M Ripplinger, Bruce Hammock, Nipavan Chiamvimonvat
Journal: Circulation (2015)

Introduction: Atrial fibrillation (AF) represents one of the most common arrhythmias seen clinically and is associated with a significant increase in morbidity and mortality, yet, current treatment paradigms have proven largely inadequate. Inflammation has been shown to play critical roles in the pathophysiology of AF. Soluble epoxide hydrolase (sEH) catalyzes the hydrolysis of anti-inflammatory epoxyeicosatrienoic acids to corresponding pro-inflammatory diols. We have previously shown beneficial effects of sEH inhibitors (sEHIs) in cardiac failure and in the reduction of atrial arrhythmia inducibility. The objective of this study is to elucidate the molecular mechanisms underlying the prevention of atrial arrhythmia inducibility by sEHIs. Methods: In vivo pressure-overload model was used to replicate chronic hypertension. Flow cytometry, electrophysiologic studies and optical mapping were used to determine the mechanistic roles of sEHIs on atrial fibrosis and the reversal of electrical remodeling in atrial myocytes. Results: We demonstrate positive effects of sEHI in AF prevention by reducing 1) inflammation, 2) atrial structural remodeling by suppression of atrial fibrosis and hypertrophy (Fig A-D), and 3) electrical remodeling in atrial myocytes (Fig E-G). Mechanistically, inhibition of sEH enzyme results in a more than three-fold decrease in cytokines and chemokines (n=5, p&lt;0.05), inhibition of NF-κB activation, reduction of oxidative and endoplasmic reticulum stress, and a more than five-fold decline in the phosphorylation of key signaling molecules including ERK1/2 and Smad2/3 in atrial myocytes and atrial fibroblasts (n=4, p&lt;0.05). Conclusions: This study provides insights into the underlying mechanisms leading to AF by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream molecules to a novel upstream therapeutic target by counteracting the inflammatory processes in AF.
NESARC Findings on Increased Prevalence of Marijuana Use Disorders—Consistent With Other Sources of Information
Authors: Deborah S. Hasin, Bridget Grant
Journal: JAMA Psychiatry (2016)

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Pulmonary Oxidative Stress, Reperfusion Injury and Lung Tissue Damage During Cardiac Surgery
Authors: Ishtiaq Rahman, Laura Walker, Guillaume P A Chanoit, Pamela Murison, James Hillier, Joya Pawade, Kim Dora, Timea Beleznai, Gianni D Angelini, M.Saadeh Suleiman, Raimondo Ascione
Journal: Circulation (2013)
Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques
Authors: Ann J Hessell, J Pablo Jaworski, Erin Epson, Kenta Matsuda, Shilpi Pandey, Christoph Kahl, Jason Reed, William F Sutton, Katherine B Hammond, Tracy A Cheever, Philip T Barnette, Alfred W Legasse, Shannon Planer, Jeffrey J Stanton, Amarendra Pegu, Xuejun Chen, Keyun Wang, Don Siess, David Burke, Byung S Park, Michael K Axthelm, Anne Lewis, Vanessa M Hirsch, Barney S Graham, John R Mascola, Jonah B Sacha, Nancy L Haigwood
Journal: Nature Medicine (2016)
Variation in melphalan dosing in myeloma patients undergoing high-dose chemotherapy and autotransplantation
Authors: J. Mehta, K. R. Carson, S. Trifilio, E. Vickrey, S. Allen, S. Singhal
Journal: Journal of Clinical Oncology (2008)

7047 Background: Chemotherapy doses are often reduced in obese patients to ameliorate toxicity; a practice shown to result in adverse outcome in breast cancer. The dose of melphalan used before autografting in myeloma correlates with outcome. Because melphalan is widely distributed in the body, exposure of myeloma cells to the drug is likely dependent upon the actual body weight (ABW). We evaluated variability in melphalan dose received by patients in terms of mg/kg ABW and ideal body weight (IBW). Methods: Data on 243 autotransplants for myeloma after 200 mg/m2 melphalan were analyzed retrospectively. The weight value used to calculate body surface area (BSA) using the Dubois formula was the ABW if it was lower than or up to 20% higher than IBW (non-obese). If ABW was >20% above IBW (obese), the value used for BSA calculation was IBW + 25–50% of the difference between ABW and IBW. Results: 191 patients were obese (ABW 20.2% to 104.7% higher than IBW; median 42.8% higher) and 92 were non-obese (ABW 18.3% lower than to 19.5% higher than IBW; median 9.0% higher). The melphalan dose administered was 2.9–6.2 mg/kg ABW (median 4.5) and 4.6–7.5 mg/kg IBW (median 5.6). There was no correlation between the mg/kg IBW and mg/kg ABW doses (r=0.10; P=0.12). The median dose for the obese group was significantly lower than the non-obese group when calculated by ABW (4.0 vs 5.0 mg/kg; range 2.9–5.5 vs 4.4–6.2; P<0.0001). The median dose was higher for the obese group when calculated by IBW (5.8 vs 5.5 mg/kg; range 5.0–7.5 vs 4.6–6.3; P<0.0001). There was a strong inverse correlation (r=0.90; P<0.0001) between the per cent ABW-IBW difference and the melphalan dose in mg/kg ABW - consistent with decreasing drug exposure as the degree of obesity increased. Expectedly, there was a modest direct correlation (r=0.49; P<0.0001) between the per cent ABW-IBW difference and the melphalan dose in mg/kg IBW. Conclusions: The dose of melphalan measured in mg/kg ABW is significantly lower in obese patients than in non-obese patients due to dose-adjustment. Further work is required to see if this affects outcome. No significant financial relationships to disclose.
Architectural adaptations of muscle to training and injury: a narrative review outlining the contributions by fascicle length, pennation angle and muscle thickness
Authors: Ryan G Timmins, Anthony J Shield, Morgan D Williams, Christian Lorenzen, David A Opar
Journal: British Journal of Sports Medicine (2016)

The architectural characteristics of muscle (fascicle length, pennation angle muscle thickness) respond to varying forms of stimuli (eg, training, immobilisation and injury). Architectural changes following injury are thought to occur in response to the restricted range of motion experienced during rehabilitation and the associated neuromuscular inhibition. However, it is unknown if these differences exist prior to injury, and had a role in injury occuring (prospectively), or if they occur in response to the incident itself (retrospectively). Considering that the structure of a muscle will influence how it functions, it is of interest to understand how these architectural variations may alter how a muscle acts with reference to the force-length and force-velocity relationships.Our narrative review provides an overview of muscle architectural adaptations to training and injury. Specifically, we (1) describe the methods used to measure muscle architecture; (2) detail the impact that architectural alterations following training interventions, immobilisation and injury have on force production and (3) present a hypothesis on how neuromuscular inhibition could cause maladaptations to muscle architecture following injury.