tbuckley/cabot-search huggingface dataset:
Pyrophosphate arthropathy: a clinical and radiological study of 105 cases.
Authors: P A Dieppe, G J Alexander, H E Jones, M Doherty, D G Scott, A Manhire, I Watt
Journal: Annals of the Rheumatic Diseases (1982)

105 consecutive patients who presented to a rheumatologist because of joint disease and who also had evidence of deposition of calcium pyrophosphate dihydrate (CPD) were studied clinically and radiologically. There were 76 women (mean age 73) and 29 men (mean age 62). Of only 18 patients below the age of 60 at presentation 12 were men. The majority of the younger male group suffered from acute attacks of synovitis, and had no clinical or radiological evidence of joint damage. In contrast the older female group had widespread destructive changes. Associated joint disease included generalised osteoarthritis (45), rheumatoid arthritis (8), joint hypermobility (13), previous knee surgery (8), and gout 92). Sixteen patients had received long-term steroid therapy. Severe destructive joint changes were seen in 16 patients. The radiological features in those with rheumatoid arthritis by ARA criteria were atypical. The relationship between CPD deposition and arthritis is discussed in the light of these findings.
Influence of Diabetes Mellitus on Inappropriate and Appropriate Implantable Cardioverter-Defibrillator Therapy and Mortality in the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Trial
Authors: Martin H. Ruwald, Wojciech Zareba, Christian Jons, Claire Zhang, Anne-Christine H. Ruwald, Brian Olshansky, Scott McNitt, Poul Erik Bloch Thomsen, Morio Shoda, Bela Merkely, Arthur J. Moss, Valentina Kutyifa
Journal: Circulation (2013)

The relationship between diabetes mellitus and risk of inappropriate or appropriate therapy in patients receiving an implantable cardioverter-defibrillator (ICD) and resynchronization therapy has not been investigated thoroughly. The effect of innovative ICD programming on therapy delivery in these patients is unknown.The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) randomized patients with a primary prophylactic ICD indication to 3 different types of ICD programming: conventional programming with a ventricular tachycardia zone of 170 to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone ≥200 bpm (arm B), or 60-second-delayed therapy (arm C). The end points of inappropriate therapy, appropriate therapy, and death were assessed among 485 patients with and 998 without diabetes mellitus. Innovative ICD programming reduced the risk of inappropriate therapy regardless of diabetes mellitus, although a trend toward a more pronounced effect of high-rate cutoff programming was seen in patients without diabetes mellitus (P for interaction=0.06). Diabetes mellitus was associated with a decreased risk of inappropriate therapy (hazard ratio, 0.54; 95% confidence interval, 0.36-0.80; P=0.002) and increased risk of appropriate therapy (hazard ratio, 1.58; 95% confidence interval, 1.17-2.14; P=0.003). In diabetic patients, there was significantly increased risk of death in those who had inappropriate therapy (hazard ratio, 4.17; 95% confidence interval, 1.52-11.40; P=0.005) and appropriate therapy (hazard ratio, 2.49; 95% confidence interval, 1.06-5.87; P=0.037) compared with those who did not.Innovative high-rate cutoff or delayed ICD programming was associated with a reduction in inappropriate therapy in patients with and without diabetes mellitus. Diabetes mellitus was associated with lower risk of inappropriate therapy but higher risk of appropriate therapy. Appropriate and inappropriate ICD therapy was associated with increased mortality in diabetic patients.URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00947310.
Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice
Authors: Siddhartha Mukherjee, Noopur Raje, Jesse A. Schoonmaker, Julie C. Liu, Teru Hideshima, Marc N. Wein, Dallas C. Jones, Sonia Vallet, Mary L. Bouxsein, Samantha Pozzi, Shweta Chhetri, Y. David Seo, Joshua P. Aronson, Chirayu Patel, Mariateresa Fulciniti, Louise E. Purton, Laurie H. Glimcher, Jane B. Lian, Gary Stein, Kenneth C. Anderson, David T. Scadden
Journal: Journal of Clinical Investigation (2008)

Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals.
Cortactin Overexpression Regulates Actin-Related Protein 2/3 Complex Activity, Motility, and Invasion in Carcinomas with Chromosome 11q13 Amplification
Authors: Brian L. Rothschild, Ann H. Shim, Amanda Gatesman Ammer, Laura C. Kelley, Kimberly B. Irby, Julie A. Head, Lin Chen, Marileila Varella-Garcia, Peter G. Sacks, Barbara Frederick, David Raben, Scott A. Weed
Journal: Cancer Research (2006)

Carcinoma cell motility and invasion are prerequisites for tumor cell metastasis, which requires regulation of the actin cytoskeleton. Cortactin is an actin-related protein 2/3 (Arp2/3) complex-activating and filamentous (F)-actin-binding protein that is implicated in tumor cell motility and metastasis, partially by its ability to become tyrosine phosphorylated. Cortactin is encoded by the CTTN gene and maps to chromosome 11q13, a region amplified in many carcinomas, including head and neck squamous cell carcinoma (HNSCC). CTTN gene amplification is associated with lymph node metastasis and poor patient outcome, and cortactin overexpression enhances motility in tumor cells lacking 11q13 amplification. However, a direct link between increased motility and invasion has not been reported in tumor cells with chromosome 11q13 amplification and cortactin overexpression. In this study, we have examined the relationship between CTTN amplification and tumor cell motility in HNSCC. In 11 of 39 (28%) HNSCC cases, cortactin overexpression determined by immunohistochemistry correlates with lymph node metastasis and CTTN gene amplification. HNSCC cells containing cortactin gene amplification and protein overexpression display increased binding and activation of Arp2/3 complex, and were more motile and invasive than HNSCC cells lacking CTTN amplification. Down-regulation of cortactin expression in CTTN-amplified HNSCC cells by small interfering RNA impairs HNSCC motility and invasion. Treatment of HNSCC cells with the epidermal growth factor receptor inhibitor gefitinib inhibits HNSCC motility and down-regulates cortactin tyrosine phosphorylation. These data suggest that cortactin may be a valid prognostic and therapeutic marker for invasive and metastatic HNSCC and other carcinomas with 11q13 amplification.
Crossing-Over in a Hypervariable Species Preferentially Occurs in Regions of High Local Similarity
Authors: Vladimir B. Seplyarskiy, Maria D. Logacheva, Aleksey A. Penin, Maria A. Baranova, Evgeny V. Leushkin, Natalia V. Demidenko, Anna V. Klepikova, Fyodor A. Kondrashov, Alexey S. Kondrashov, Timothy Y. James
Journal: Molecular Biology and Evolution (2014)

Recombination between double-stranded DNA molecules is a key genetic process which occurs in a wide variety of organisms. Usually, crossing-over (CO) occurs during meiosis between genotypes with 98.0-99.9% sequence identity, because within-population nucleotide diversity only rarely exceeds 2%. However, some species are hypervariable and it is unclear how CO can occur between genotypes with less than 90% sequence identity. Here, we study CO in Schizophyllum commune, a hypervariable cosmopolitan basidiomycete mushroom, a frequently encountered decayer of woody substrates. We crossed two haploid individuals, from the United States and from Russia, and obtained genome sequences for their 17 offspring. The average genetic distance between the parents was 14%, making it possible to study CO at very high resolution. We found reduced levels of linkage disequilibrium between loci flanking the CO sites indicating that they are mostly confined to hotspots of recombination. Furthermore, CO events preferentially occurred in regions under stronger negative selection, in particular within exons that showed reduced levels of nucleotide diversity. Apparently, in hypervariable species CO must avoid regions of higher divergence between the recombining genomes due to limitations imposed by the mismatch repair system, with regions under strong negative selection providing the opportunity for recombination. These patterns are opposite to those observed in a number of less variable species indicating that population genomics of hypervariable species may reveal novel biological phenomena.
Postprandial Hyperglycemia Is Associated With an Increase of Blood Pressure in Type 1 Diabetic Patients Treated With Continuous Subcutaneous Insulin Infusion
Authors: Giuseppe Lepore, Anna Corsi, Alessandro R. Dodesini, Italo Nosari, Roberto Trevisan
Journal: Diabetes Care (2007)

Blood pressure normally decreases after a meal and reaches a nadir between 30 and 60 min after eating (1). Giugliano et al. (2) showed that acute hyperglycemia in normal subjects significantly increases systolic and diastolic blood pressure. To define the relationship between postprandial plasma glucose excursions and blood pressure variations in type 1 diabetes, we studied 10 normotensive, type 1 diabetic patients (mean ± SD age 39.7 ± 16.7 years, diabetes duration 10.5 ± 5.4 years, A1C 7.4 ± 0.8%, and BMI 23.9 ± 3.5 kg/m2) without microangiopatic complications. All patients were in therapy with continuous subcutaneous insulin infusion. None took any hypotensive drug. …
New Roles of Carboxypeptidase E in Endocrine and Neural Function and Cancer
Authors: Niamh X. Cawley, William C. Wetsel, Saravana R. K. Murthy, Joshua J. Park, Karel Pacak, Y. Peng Loh
Journal: Endocrine Reviews (2012)

Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin precursors to generate enkephalin. Since then, CPE has been shown to be a multifunctional protein that subserves many essential nonenzymatic roles in the endocrine and nervous systems. Here, we review the phylogeny, structure, and function of CPE in hormone and neuropeptide sorting and vesicle transport for secretion, alternative splicing of the CPE transcript, and single nucleotide polymorphisms in humans. With this and the analysis of mutant and knockout mice, the data collectively support important roles for CPE in the modulation of metabolic and glucose homeostasis, bone remodeling, obesity, fertility, neuroprotection, stress, sexual behavior, mood and emotional responses, learning, and memory. Recently, a splice variant form of CPE has been found to be an inducer of tumor growth and metastasis and a prognostic biomarker for metastasis in endocrine and nonendocrine tumors.
Morphology and Histogenesis of Anal Region and Clitoral Gland Tumors Induced in Mice by 1,2-Dimethylhydrazine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: V S Turusov
Journal: JNCI Journal of the National Cancer Institute (1980)

Ninety-seven tumors induced in the anal region in female CBA and BALB/c mice by 1,2-dimethylhydrazine were examined histologically. Tumors originated mainly from the following sources: epidermis (papillomas and basal cell neoplasms), pilosebaceous complexes of the anal region (keratoacanthomas, cystic squamous cell tumors, and adenomas of the perianal sebaceous glands), and clitoral (preputial) glands (adenomas and adenoacanthomas). A subcutaneous location and late ulceration were characteristics of many tumors originating from the pilosebaceous complexes and clitoral glads. From 31 to 43% of all anal tumors were of sebaceous gland (perianal or clitoral) origin. Cystic squamous cell tumors were morphologically similar to type II keratoacanthomas of rodents. Squamous cell tumors of any origin finally became squamous carcinomas.
The flow-volume loop: reproducibility of air and helium-based tests in normal subjects
Authors: J B Macdonald, T J Cole
Journal: Thorax (1980)

A statistical technique new to lung function testing is described and has been applied to a study of flow-volume loop tests in normal subjects. Maximal expiratory flow-volume loops were performed on air, then breathing an 80% helium: 20% oxygen mixture for three deep breaths (3B) then three minutes (3M) twice daily for five consecutive days on 25 asymptomatic subjects (eight smokers and 17 non-smokers). The tests were performed on an Ohio differentiating spirometer and recorded on a storage oscilloscope. The standard lung function tests—forced vital capacity (FVC), forced expiratory volume in one second (FEV<sub>1</sub>) and peak expiratory flow rate (PEFR)—were the most reproducible. Maximal expiratory flow rate at 50% vital capacity (MEF<sub>50</sub>) and at 75% vital capacity (MEF<sub>75</sub>) were passably reproducible. MEF<sub>50</sub> and MEF<sub>75</sub> were as reliable breathing helium as breathing air, with 3B as reliable as 3M. However ratios of MEF helium/MEF air were very unreliable indeed, for both MEF<sub>50</sub> and MEF<sub>75</sub> and 3B and 3M. Thus percentage improvement in MEF after breathing helium appears to be an unreliable test in normal subjects. Helium isoflow volume was also very poorly reproducible with, on average, more variation within a single subject than between subjects. These conclusions apply to normal subjects and will require further work to assess them in specific diseases. However the very poor performance of isoflow volume and flow ratios in normal subjects suggests that it may be relatively difficult to distinguish normal subjects from patients with small airways obstruction using these tests. An application of canonical variate analysis to the data is described. This statistical technique assesses which indices or combinations of indices vary independently and hence are measuring qualitatively different parameters. Almost all the data variation was encompassed by variations in four parameters. Thus there are probably only four features in the flow-volume curve which can be used to discriminate between individuals. Repeating this analysis in patients with a specific disease should enable the best tests for use in that particular disease to be defined precisely. Canonical variate analysis should also be a useful method of assessing a new lung function test, since it assesses a test9s reliability and more importantly whether it contributes any new information not given by older tests.
Exercise-induced airway narrowing in army recruits with a history of childhood asthma
Authors: DG Sinclair, MM Sims, NA Hoad, CR Winfield
Journal: European Respiratory Journal (1995)

The aim of this study was to determine whether the addition of cold, dry, inspired air to maximum heart rate (MHR) exercise increased the number of subjects demonstrating abnormal airway narrowing, when applied to symptom-free army recruits with a history of asthma in childhood. One hundred recruits with a history of asthma in childhood underwent two exercise challenges to maximum heart rate, breathing either room air or cold dry air in randomized order. The percentage fall index (%FI) was calculated for each challenge, a positive result being &gt; or = 15%. A total of 29 subjects had a positive % fall index, 12 subjects were positive to both challenges, 7 to the room air alone and 10 to the cold air challenge alone. In these subjects (n = 29), the mean (SD) % fall index to the cold air challenge was 22.7 (11.0)% compared with 16.3 (9.5)% for the room air challenge. We conclude that when employed as a screening test for abnormal airway narrowing, the addition of cold, dry, inspired air during exercise does not increase the number of subjects with a positive response, but the magnitude of the response is increased.
Prenatal nicotine increases pulmonary α7 nicotinic receptor expression and alters fetal lung development in monkeys
Authors: Harmanjatinder S. Sekhon, Yibing Jia, Renee Raab, Alexander Kuryatov, James F. Pankow, Jeffrey A. Whitsett, Jon Lindstrom, Eliot R. Spindel
Journal: Journal of Clinical Investigation (1999)

It is well established that maternal smoking during pregnancy is a leading preventable cause of low birth weight and prematurity. Less appreciated is that maternal smoking during pregnancy is also associated with alterations in pulmonary function at birth and greater incidence of respiratory illnesses after birth. To determine if this is the direct result of nicotine interacting with nicotinic cholinergic receptors (nAChRs) during lung development, rhesus monkeys were treated with 1 mg/kg/day of nicotine from days 26 to 134 of pregnancy. Nicotine administration caused lung hypoplasia and reduced surface complexity of developing alveoli. Immunohistochemistry and in situ α-bungarotoxin (αBGT) binding showed that α7 nAChRs are present in the developing lung in airway epithelial cells, cells surrounding large airways and blood vessels, alveolar type II cells, free alveolar macrophages, and pulmonary neuroendocrine cells (PNEC). As detected both by immunohistochemistry and by αBGT binding, nicotine administration markedly increased α7 receptor subunit expression and binding in the fetal lung. Correlating with areas of increased α7 expression, collagen expression surrounding large airways and vessels was significantly increased. Nicotine also significantly increased numbers of type II cells and neuroendocrine cells in neuroepithelial bodies. These findings demonstrate that nicotine can alter fetal monkey lung development by crossing the placenta to interact directly with nicotinic receptors on non-neuronal cells in the developing lung, and that similar effects likely occur in human infants whose mothers smoke during pregnancy.
Pathogenesis and Host Control of Gammaherpesviruses: Lessons from the Mouse
Authors: Erik Barton, Pratyusha Mandal, Samuel H. Speck
Journal: Annual Review of Immunology (2011)

Gammaherpesviruses are lymphotropic viruses that are associated with the development of lymphoproliferative diseases, lymphomas, as well as other nonlymphoid cancers. Most known gammaherpesviruses establish latency in B lymphocytes. Research on Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68/γHV68/MHV4) has revealed a complex relationship between virus latency and the stage of B cell differentiation. Available data support a model in which gammaherpesvirus infection drives B cell proliferation and differentiation. In general, the characterized gammaherpesviruses exhibit a very narrow host tropism, which has severely limited studies on the human gammaherpesviruses EBV and Kaposi's sarcoma–associated herpesvirus. As such, there has been significant interest in developing animal models in which the pathogenesis of gammaherpesviruses can be characterized. MHV68 represents a unique model to define the effects of chronic viral infection on the antiviral immune response.
Targeting Autophagy Augments <i>In Vitro</i> and <i>In Vivo</i> Antimyeloma Activity of DNA-Damaging Chemotherapy
Authors: Yaozhu Pan, Ying Gao, Liang Chen, Guangxun Gao, Hongjuan Dong, Yang Yang, Baoxia Dong, Xiequn Chen
Journal: Clinical Cancer Research (2011)

Although autophagy occurs in most tumor cells following DNA damage, it is still a mystery how this DNA-damaging event turns on the autophagy machinery in multiple myeloma (MM) and how the functional status of autophagy impacts on its susceptibility to death in response to DNA-damaging chemotherapy.We investigate the effects of DNA damage on autophagy in MM cells and elucidate its underlying molecular mechanism. Then, we examined the impacts of pharmacologic or genetic inhibition of autophagy on DNA damage-induced apoptosis. Furthermore, the antimyeloma activity of autophagy inhibitor in combination with DNA-damaging agents was evaluated in MM xenograft models.We showed that DNA-damaging drugs, doxorubicin and melphalan, induce caspase-dependent apoptosis and concurrently trigger Beclin 1-regulated autophagy in human MM cell lines H929 and RPMI 8226. Mechanistically, association of autophagy execution proteins Beclin 1 with class III phosphoinositide 3-kinase, which is inhibited by Bcl-2 recruitment, contributes directly to the autophagic process. Importantly, targeting suppression of autophagy by minimally toxic concentrations of pharmacologic inhibitors (hydroxychloroquine and 3-methyladenine) or short hairpin RNAs against autophagy genes, Beclin 1 and Atg5, dramatically augments proapoptotic activity of DNA-damaging chemotherapy both in vitro using MM cell lines or purified patient MM cells and in vivo in a human plasmacytoma xenograft mouse model.These data can help unravel the underlying molecular mechanism of autophagy in DNA-damaged MM cells and also provide a rationale for clinical evaluation of autophagy inhibitors in combination with DNA-damaging chemotherapy in MM.
US oncologists update guidance on DNA sequencing in clinical practice
Authors: Michael McCarthy
Journal: BMJ (2015)

Oncologists must exercise care as they incorporate new DNA sequencing technologies into clinical practice to maximize their benefits and minimize the potential harms, the American Society of Clinical Oncology has said in an updated policy statement on genetic and genomic testing for cancer susceptibility.1

Technologies such as massive parallel sequencing now make it possible for clinicians to sequence ever larger panels of genes and even whole genomes relatively cheaply. As a result, many oncologists are using DNA sequencing in a process called somatic mutation profiling to identify acquired sequence variations …
Vδ2-Jα rearrangements are frequent in precursor-B–acute lymphoblastic leukemia but rare in normal lymphoid cells
Authors: Tomasz Szczepański, Vincent H. J. van der Velden, Patricia G. Hoogeveen, Maaike de Bie, Daniëlle C. H. Jacobs, Elisabeth R. van Wering, Jacques J. M. van Dongen
Journal: Blood (2003)
Carcinoma of the Bronchus with Bence Jones Proteinuria
Authors: J. T. Hughes
Journal: BMJ (1954)

SununaryThe efliects of intravenous injection of 25-50 mg. of promethazine hydrochloride have been studied in six cases undergoing cardiac catheterization.No signifi- cant changes occurred in the systemic blood pressure.One case showed a slight rise in pulmonary artery pres- sure.Pulmonary blood-flow showed little change in four cases, an increase in one, and a slight decrease in one.The heart rate increased in all cases.The small circulatory changes associated with a satisfactory hypnotic effect suggest that promethazine is a suitable drug for the premedication of cardiac cases.We are indebted to the technical staff of the Institute of Cardiology for assistance in making these observations.