tbuckley/cabot-search huggingface dataset:
Incidence of Late-Relapse Germ Cell Tumor and Outcome to Salvage Chemotherapy
Authors: Ellen A. Ronnen, G. Varuni Kondagunta, Jennifer Bacik, Stephanie Marion, Dean F. Bajorin, Joel Sheinfeld, George J. Bosl, Robert J. Motzer
Journal: Journal of Clinical Oncology (2005)

Purpose To define the incidence, clinical features, and outcome to salvage chemotherapy in patients with late-relapse germ cell tumor (GCT) after a complete response to first-line chemotherapy. Patients and Methods Two patient populations were examined. First, retrospective analysis of 246 patients treated on a clinical trial with salvage chemotherapy was performed; 29 patients with late-relapse GCT were identified and evaluated for treatment outcome and survival. Salvage regimens included paclitaxel, ifosfamide, and cisplatin, single agents, or a high-dose chemotherapy program. Second, the incidence of late relapse was assessed by retrospective analysis of 551 patients after a complete response (CR) to first-line chemotherapy. Results Twenty-nine patients received salvage chemotherapy on a clinical trial for late relapse GCT. The median survival was 23.9 months. At a median follow-up of 50.6 months, there were nine survivors. The chemotherapy regimens varied, but the only CRs were observed in patients treated with paclitaxel, ifosfamide, and cisplatin. Seven (50%) of 14 patients treated with paclitaxel, ifosfamide, and cisplatin achieved a continuous CR. Among the second population of 551 patients who had previously achieved a CR to a first-line chemotherapy trial, 17 were identified as having a late relapse (3%). The median time to relapse for these 17 patients was 7.8 years. Conclusion Late-relapse GCT is uncommon and is associated with a poor prognosis resulting from a high degree of resistance to chemotherapy. Chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by surgery may be effective in patients with late-relapse GCT who are not considered candidates for primary surgery.
A FILTERABLE VIRUS INFECTION OF RABBITS
Authors: C. Philip Miller, C. H. Andrewes, Homer F. Swift
Journal: The Journal of Experimental Medicine (1924)

1. Blood and joint fluid of patients suffering from rheumatic fever were inoculated into the testicles of rabbits, and transfers were made from testicle to testicle at varying intervals. In three series, in none of which were the periods between the transfers longer than 4 days, a virus was recovered which produced acute orchitis in rabbits. The virus could be indefinitely propagated from rabbit to rabbit. 2. Intradermal inoculation of the virus led to the appearance of raised erythematous lesions in 3 to 6 days. 3. Intrathoracic inoculations near the heart led to a fibrinous pericarditis in three out of five rabbits, and to a myocarditis in one. 4. Nuclear inclusion bodies staining pink with eosin were found in the lesions in the testis, skin, pericardium, and heart muscle. 5. Rabbits inoculated into skin or testes were refractory, 2 weeks later, to further intradermal inoculations; after this interval their serum had developed the power to neutralize the virus in vitro. 6. The virus can be preserved in 50 per cent glycerol for at least 18 days. It can be preserved after freezing and drying for at least 8 days and probably for 10 weeks. 7. Cross-immunity tests point to the identity of the virus with that described by Rivers and Tillett in their studies on chicken-pox as Virus III. 8. These facts together with the failure of rheumatic fever sera to neutralize the virus indicate that it bears no etiologic relationship to rheumatic fever.
MELANOMA (SARCOMA) OF THE EYE IN A SYPHILITIC RABBIT
Authors: Wade H. Brown, Louise Pearce
Journal: The Journal of Experimental Medicine (1926)

A melanotic tumor developed in a defective eye of a syphilitic rabbit following repeated genital inoculations with Treponema pallidum. The appearance of the tumor coincided with the development of a syphilitic lesion in the same eye, suggesting a relation between the occurrence of the two lesions.
Reduction of peripheral blood lymphocytes in patients receiving gold therapy for rheumatoid arthritis.
Authors: J G Hanly, B Bresnihan
Journal: Annals of the Rheumatic Diseases (1985)

Peripheral blood lymphocytes were monitored prospectively in 10 patients with rheumatoid arthritis (RA) receiving up to 1 g of sodium aurothiomalate. There was a significant fall in the absolute lymphocyte count from a mean +/- SEM of 1956 +/- 190/mm3 (1.956 +/- 0.19 X 10(9)/l) to 1232 +/- 210/mm3 (1.232 +/- 0.21 X 10(9)/l) (p less than 0.01). The number of of circulating lymphocytes fell in all patients by an amount which ranged between 108/mm3 (0.108 X 10(9)/l) and 1394/mm3 (1.394 X 10(9)/l), with a mean fall of 727/mm3 (0.727 X 10(9)/l). No significant change was noted in the total white cell count or total polymorphonuclear cell count over the same period. In contrast there was no change in the total lymphocyte count in an age and sex matched group of RA patients treated with penicillamine. This previously unreported observation may give new insight into the mechanism of action of gold salts in RA.
Upregulation of Phosphodiesterase-4 in the Lung of Allergic Rats
Authors: Hui-Fang Tang, Yan-Hua Song, Jun-Chun Chen, Ji-Qiang Chen, Peng Wang
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Inhibitors of phosphodiesterase-4 (PDE4) are efficacious for allergic asthma in animal models and have shown some efficacy in human asthma. Regulation of PDE4 in allergy and asthma has been widely investigated in blood leukocytes, with discrepant results. This study investigated PDE4 regulation in the lung in a rat model of allergic asthma. Ovalbumin sensitization and challenge significantly increased pulmonary resistance and lung interleukin (IL)-4 production. The increases in pulmonary resistance and IL-4 production were both suppressed by the PDE4-selective inhibitor rolipram or the corticosteroid drug dexamethasone. Furthermore, cAMP-PDE enzyme activity in the lung was also significantly increased by the sensitization and challenge. mRNA analysis confirmed that PDE4 gene expression was increased in the lung of the allergic rats. A highly significant correlation was observed between the increases in PDE activity and IL-4 production. Our data suggest, for the first time, that PDE4 may be upregulated in the lung and play a role in the pathogenesis of allergic asthma.
A Population-Based Study of the Risk of Diabetic Retinopathy in Patients With Type 1 Diabetes and Celiac Disease
Authors: Kaziwe Mollazadegan, Maria Kugelberg, Scott M. Montgomery, David S. Sanders, Johnny Ludvigsson, Jonas F. Ludvigsson
Journal: Diabetes Care (2012)

Celiac disease (CD) is associated with type 1 diabetes (T1D). In the current study, we examined whether CD affects the risk of diabetic retinopathy (DRP) in patients with T1D.This was a population-based cohort study. Through the Swedish National Patient Register, we identified 41,566 patients diagnosed with diabetes in 1964-2009 and who were ≤30 years of age at diagnosis. CD was defined as having villous atrophy (Marsh stage 3) according to small intestinal biopsies performed between 1969 and 2008, with biopsy reports obtained from Sweden's 28 pathology departments. During follow-up, 947 T1D patients had a diagnosis of CD. We used Cox regression analysis with CD as a time-dependent covariate to estimate adjusted hazard ratios (aHRs) for DRP in patients with T1D and CD and compared them with patients with T1D but no CD.Duration of CD correlated with the risk of DRP. When results were stratified by time since CD diagnosis, individuals with T1D and CD were at a lower risk of DRP in the first 5 years after CD diagnosis (aHR 0.57 [95% CI 0.36-0.91]), followed by a neutral risk in years 5 to <10 (1.03 [0.68-1.57]). With longer follow-up, coexisting CD was a risk factor for DRP (10 to <15 years of follow-up, aHR 2.83 [95% CI 1.95-4.11]; ≥15 years of follow-up, 3.01 [1.43-6.32]).Having a diagnosis of CD for >10 years is a risk factor for the development of DRP in T1D. Long-standing CD in patients with T1D merits intense monitoring of DRP.
Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial
Authors: Roxana Mehran, Alexandra J Lansky, Bernhard Witzenbichler, Giulio Guagliumi, Jan Z Peruga, Bruce R Brodie, Dariusz Dudek, Ran Kornowski, Franz Hartmann, Bernard J Gersh, Stuart J Pocock, S Chiu Wong, Eugenia Nikolsky, Louise Gambone, Lynn Vandertie, Helen Parise, George D Dangas, Gregg W Stone
Journal: The Lancet (2009)
Impaired removal of 8-hydroxydeoxyguanosine induced by UVB radiation in naevoid basal cell carcinoma syndrome cells
Authors: C. Nishigori, Y. Arima, Y. Matsumura, M. Matsui, Y. Miyachi
Journal: British Journal of Dermatology (2005)

The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis such as multiple basal cell carcinomas, odontogenic keratocysts and developmental abnormalities such as calcified dural folds and rib-anomalies. Recently, it has been shown that ultraviolet (UV) B exposure produced more BCCs in ptch knockout mice than wild mice.To Investigate the role of UV in development of BCCs in NBCCS, cellular sensitivity to killing by UVB and removal of UVB-induced oxidative DNA damage were examined using fibroblasts derived from patients with NBCCS under physiologically relevant doses of UVB exposure.Three patients with NBCCS, a 59-year-old male patient, an 18-year-old boy and a 13-year-old boy were examined by photobiological analysis. Cellular sensitivity to killing by UVB and UVC and removal of oxidative DNA damage caused by UVB were tested using fibroblasts derived from these patients. We measured cellular 8-hydroxydeoxyguanosine (8-OHdG) after UVB exposure up to 24 h after UVB exposure using high-performance liquid chromatography.All three cell strains derived from the patients with NBCCS were hypersensitive to killing by UVB (D10: 50-70% of normal) but not by UVC. After UVB exposure, the production of 8-OHdG increased dose dependently up to 3200 J m-2 in both NBCCS cells and normal cells. In normal cells, 8-OHdG after UVB exposure returned to its basal level during 24 h, whereas in NBCCS cells the amount of 8-OHdG after 800 J m-2 of UVB exposure did not return to its basal level even after 24 h. The result indicates the removal of 8-OHdG could be impaired in NBCCS cells. Ability in removal of thymine dimers of NBCCS cells was similar to that of normal cells.Hypersensitivity to UVB can be one of the diagnostic tools of NBCCS for those whose clinical features have not yet completed. Hypersensitivity to cell killing and the impairment of removal of 8-OHdG after UVB exposure may play some role in developing BCCs and other tumours in NBCCS.
YAP IS A CRITICAL AND NOVEL REGULATOR OF MIGRATION AND INVASION AND PREDICTS POOR OUTCOME IN GLIOBLASTOMA
Authors: A. Quinones-Hinojosa, S. R. Shah, J. Park, A. Levchenko, A. Quinones-Hinojosa
Journal: Neuro-Oncology (2014)

BACKGROUND: Cell migration plays a pivotal role during tissue morphogenesis and homeostasis in multi-cellular organisms. By integrating extracellular cues and intracellular signaling, migration ensures the organized spatial distribution of cells. One of the hallmarks of tumor malignancy is the ability of cells to not only locally invade its surrounding parenchyma but also distally metastasize. Thus, tumors often display a collective sheet of migrating cells which may eventually disseminate and migrate in a single cell manner. To model this phenomenon, we studied the underlying mechanism controlling collective and single cell migration. METHODS: We studied collective and single cell migration in a nanogrooved substratum which mimics reorganized fibrous structures of extracellular matrix. We used our in vivo murine intracranial xenograft model using human GBM cells to study the role of YAP in driving invasive tumor growth. We studied if the YAP-driven cell dispersal mechanisms confer poor patient prognosis in the TCGA and REMBRANDT GBM databases. RESULTS: Using a nanogrooved substratum we observed an epithelial-to-mesenchymal transition-like (EMT-like) behavior with formation of finger-like structures with faster moving marginal cells at the sheet edge. Cells at the tip of these structures frequently lost contact with neighboring cells and disseminated from the original collective cell sheet, which was accompanied by the expression of EMT markers (vimentin and the nuclear translocation of β-catenin). Recently, Yes-associated protein (YAP), a mechanosensor and transcriptional regulator, has been implicated in potentiating migration, invasion, and metastasis; however, the underlying mechanisms remain poorly understood. We observed that YAP is activated in these finger-like projections. We explored mechanisms of YAP-mediated migration and invasion in normal cells and cancer cells where YAP is hyperactive. We found that YAP plays a pivotal role in regulation of this complex migratory and invasive behavior through a novel small Rho-GTPase-dependent signaling mechanism. As with glioblastoma (GBM), metastatic cancers often evade detection because individual cells spread from the primary bulk tumor; thus, making complete resection and treatment impossible. Congruent with our in vitro studies, our in vivo murine model demonstrates the role of YAP in driving invasive tumor growth. We show that these YAP-driven cell dispersal mechanisms confer poor patient prognosis in the TCGA and REMBRANDT GBM databases. CONCLUSIONS: Our findings provide new insights into the biology of aggressive cancers with particular prognostic relevance of this YAP-driven pro-migration and invasion cascade in glioblastoma. In addition, our studies suggest these YAP-dependent mechanisms are evolutionary conserved during development and regeneration and are co-opted by pathological diseases. SECONDARY CATEGORY: Neuropathology & Tumor Biomarkers.
Development of a new in situ hybridization method for the detection of global bacterial DNA to provide early evidence of a bacterial infection in spontaneous bacterial peritonitis
Authors: Hirayuki Enomoto, Shin-ichi Inoue, Akio Matsuhisa, Nobuhiro Aizawa, Hiroyasu Imanishi, Masaki Saito, Yoshinori Iwata, Hironori Tanaka, Naoto Ikeda, Yoshiyuki Sakai, Tomoyuki Takashima, Soji Shimomura, Hiroko Iijima, Hideji Nakamura, Shuhei Nishiguchi
Journal: Journal of Hepatology (2011)
Plasma Renin Activity and Urinary Sodium Excretion as Prognostic Indicators in Nonazotemic Cirrhosis with Ascites
Authors: VICENTE ARROYO
Journal: Annals of Internal Medicine (1981)

Azotemia is an ominous prognostic sign in cirrhosis with ascites. To investigate whether other renal disturbances are also prognostically significant, we studied the renin-aldosterone system and sodium excretion (UNaV) in 75 patients who had nonazotemic cirrhosis with ascites and related these to survival. On the basis of plasma renin activity patients were classified in two groups. Group I included 34 patients with normal renin activity (1.13 +/- 0.69 ng/mL . h) and Group II, 41 patients with high renin activity (7.46 +/- 3.86 ng/mL . h). The two groups differed significantly (p less than 0.001) in plasma aldosterone, UNaV, and wedged hepatic venous pressure but not in clinical features, liver function, glomerular filtration, and renal plasma flow. Patients of Group I lived significantly longer than those of Group II (the 50% survival rates were 28 months and 6 months, respectively). Survival curves obtained after grouping the patients according to UNaV (higher and lower than 10 meq/d) were almost identical to those obtained according to renin activity. The study results indicate that plasma renin activity and UNaV are of prognostic value in nonazotemic cirrhosis with ascites.
Metastatic ocular deposits due to bronchial carcinoma
Authors: C. C. Evans, A. J. Mearns, J. Delaney, W. A. Littler
Journal: Thorax (1971)

Three case reports of patients with bronchial carcinoma who presented with visual disturbances due to ocular metastases are described. The reasons for the rarity of this syndrome are discussed and its frequent association with cerebral metastases is explained. Cytotoxic drugs provide short-term effective therapy.
Cost-effectiveness of video-assisted thoracoscopic surgery versus conservative treatment for first time or recurrent spontaneous pneumothorax
Authors: FM Schramel, TG Sutedja, JC Braber, JC van Mourik, PE Postmus
Journal: European Respiratory Journal (1996)

The aim of this study was to analyse differences in efficacy and costs in treating first time or recurrent spontaneous pneumothorax by conservative therapy (pleural drainage or observation) and video-assisted thoracoscopic surgery (VATS). Retrospectively, 112 patients treated by conservative therapy during 1985-1989 (Period 1) were compared with 97 patients treated by VATS during 1991-1994 (Period 2). Mean follow-up time in each period was more than 2 yrs. Patients in both periods had comparable clinical characteristics. Irrespective of first time or recurrent spontaneous pneumothorax at presentation, drainage and hospitalization times were longer, and complication and recurrence rates were higher in Period 1. When costs due to the waiting time before VATS were excluded, the total costs in Period 1 were higher than in Period 2. Video-assisted thoracoscopic surgery is more effective in treating patients with first time or recurrent spontaneous pneumothorax, with less morbidity and total costs compared to conservative therapy. In view of cost-effectiveness, we feel that a different management of first time or recurrent spontaneous pneumothorax is not justified.
Excitation-Contraction Coupling in Rabbit Aorta Studied by the Lanthanum Method for Measuring Cellular Calcium Influx
Authors: CORNELIS VAN Breemen, BLANCA R. FARINAS, PEGGY GERBA, ELIZABETH D. MCNAUGHTON
Journal: Circulation Research (1972)

Lanthanum inhibits 45 Ca efflux from internally injected squid axons. Evidence for La 3+ blockade of Ca 2+ fluxes across the cell membrane was also obtained for aortic smooth muscle: 1mM La 3+ completely inhibited contractions which otherwise resulted from adding Ca 2+ to calcium-free depolarizing solutions, and 2 mM La 3+ caused a 50% inhibition of the late 45 Ca efflux. Ca 2+ bound extracellularly could be displaced by La 3+ , and the binding sites preferred La 3+ over Ca 2+ . We could thus use La 3+ to eliminate extracellular bound Ca 2+ from our calcium-influx measurements as follows: after exposure of the aortic strips to experimental solutions labeled with 45 Ca, the extracellular Ca 2+ label was displaced by putting the strips in a calcium-free solution containing 2 mM La 3+ for 60 minutes. The loss of intracellular Ca 2+ was minimized during this hour by the La 3+ blockade of Ca 2+ membrane fluxes. Tissue weight, 45 Ca, and total Ca 2+ were then measured using standard techniques. Studies employing this new method showed that depolarization by high K + , Na + replacement, and high pH activate smooth muscle contraction by stimulating Ca 2+ influx. Low pH and La 3+ block Ca 2+ influx. Norepinephrine initiates aortic contractions by release of intracellularly sequestered Ca 2+ . Angiotensin and histamine appear to release Ca 2+ from this same fraction.
Upper airway cooling reduces upper airway resistance in anaesthetized young guinea-pigs
Authors: AK Curran, KD O'Halloran, A Bradford
Journal: European Respiratory Journal (1998)

In adults, the upper airway (UA) contains a variety of receptors including cold receptors, which evoke reflex effects on ventilation and UA dilator muscle activity, which may be important in the regulation of UA patency. However, very little is known about UA receptors in young animals, and the effects of UA cooling on UA dilator muscle activity and resistance have not been studied. A constant flow of warm or cool air was applied to the isolated UA in anaesthetized, vagotomized young guinea-pigs breathing spontaneously through a low-cervical tracheostomy while ventilation, UA resistance and geniohyoid muscle electromyographic activity were recorded. Cooling caused an inhibition of breathing, a reduction in UA resistance and an excitation of geniohyoid muscle activity. Topical anaesthesia of the UA or sealing the nose and cutting the superior laryngeal and glossopharyngeal nerves abolished the ventilatory and geniohyoid muscle responses but not the fall in UA resistance. It is concluded that upper airway cooling reflexly inhibits breathing and excites geniohyoid muscle activity. Cooling also reduces upper airway resistance by an effect which is not of reflex origin, possibly by reducing upper airway mucosal blood flow.
Human rhinovirus infection during naturally occurring COPD exacerbations
Authors: Sîobhán N. George, Davinder S. Garcha, Alexander J. Mackay, Anant R.C. Patel, Richa Singh, Raymond J. Sapsford, Gavin C. Donaldson, Jadwiga A. Wedzicha
Journal: European Respiratory Journal (2014)

Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the time-course of HRV infection in naturally occurring exacerbations is unknown. Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae , Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified. HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p&lt;0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p=0.046) or sore throats (p=0.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02–5.30) per year compared with patients without HRV (2.51 (2.00–3.51)) (p=0.038). HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies.
Immune Suppression Feature of Ursodeoxycholic Acid is DC-mediated as Measured in Eosinophilic Airway Inflammation Model
Authors: A. KleinJan, M.A. Willart, H. Hammad, M. van Nimwegen, L. Moons, H.C. Hoogsteden, B.N. Lambrecht
Journal: Journal of Allergy and Clinical Immunology (2009)
Response to Letter Regarding Article, “Prognostic Modeling of Individual Patient Risk and Mortality Impact of Ischemic and Hemorrhagic Complications: Assessment From the Acute Catheterization and Urgent Intervention Triage Strategy Trial”
Authors: Gregg W. Stone, Roxana Mehran, Eugenia Nikolsky, Helen Parise, Martin Fahy, Alexandra J. Lansky, Jeffrey W. Moses, Stuart J. Pocock, Tim C. Clayton, Michel E. Bertrand, A. Michael Lincoff, E. Magnus Ohman, Harvey D. White
Journal: Circulation (2010)
Response to Antiretroviral Therapy after a Single, Peripartum Dose of Nevirapine
Authors: Shahin Lockman, Roger L. Shapiro, Laura M. Smeaton, Carolyn Wester, Ibou Thior, Lisa Stevens, Fatima Chand, Joseph Makhema, Claire Moffat, Aida Asmelash, Patrick Ndase, Peter Arimi, Erik van Widenfelt, Loeto Mazhani, Vladimir Novitsky, Stephen Lagakos, Max Essex
Journal: New England Journal of Medicine (2007)

A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants.