tbuckley/cabot-search huggingface dataset:
Definition, Diagnosis, and Management of Intravascular Large B-Cell Lymphoma: Proposals and Perspectives From an International Consensus Meeting
Authors: Maurilio Ponzoni, Andrés J.M. Ferreri, Elías Campo, Fabio Facchetti, Luca Mazzucchelli, Tadashi Yoshino, Takuhei Murase, Stefano A. Pileri, Claudio Doglioni, Emanuele Zucca, Franco Cavalli, Shigeo Nakamura
Journal: Journal of Clinical Oncology (2007)

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of diffuse LBCL characterized by preferential intravascular growth of malignant lymphocytes, aggressive behavior, and an often fatal course. IVLBCL usually affects elderly patients with poor performance status, elevated lactic dehydrogenase serum levels, anemia, and B symptoms. It displays some differences in clinical presentation among diverse geographical areas, mostly between patients diagnosed in Western countries and Japan. In addition, data from the literature suggest that pathologic diagnostic criteria as well as clinical features of this disease may be broader than described in current classification scheme(s). Under the sponsorship of the International Extranodal Lymphoma Study Group, clinicians and pathologists with interest in IVLBCL, coming from Western and Eastern countries, joined to reach a consensus on defining features as well as to focus on the most urgent unresolved issues in IVLBCL. To this end, a representative group of IVLBCL patients coming from both the aforementioned geographical areas were collectively analyzed. Additional features of IVLBCL were proposed both under clinical and pathologic stand points. At the meeting, it emerged that IVLBCL may have additional histopathologic/cytologic definition criteria with respect to those currently recommended, some clinical features are not randomly distributed worldwide, recent therapeutic approaches, such as anti-CD20-containing regimens, may improve outcome, and kidney, spleen, and liver involvement may show peculiar histopathologic features. Finally, a provisional practical diagnostic approach to hemophagocytosis-associated patients and a proposal for the most useful criteria in the settings of differential diagnosis are included.
Accessory and stimulating properties of dendritic cells and macrophages isolated from various rat tissues
Authors: WEF Klinkert, JH LaBadie, WE Bowers
Journal: The Journal of Experimental Medicine (1982)

Single cell suspensions of rat lymphoid and nonlymphoid tissues were fractionated on discontinuous gradients of bovine serum albumin into high density and low density subfractions. In general, accessory activity required for responses of periodate-treated T lymphocytes was recovered only in a low density population containing a small percent of the total fractionated cells from lymph nodes, spleen, liver, skin, and peritoneal exudates. Further purification always led to an increase of both accessory activity and number of dendritic cells present in nonrosetting and nonadherent populations. After purification, a high recovery of the total accessory activity was found in fractions that contained a high percentage of dendritic cells resulting in a more than 1,000-fold enrichment in accessory activity per cell. No other fraction obtained during the purification contained significant accessory activity. In all cases, macrophage-enriched populations lacked accessory cell activity. With the exception of peritoneal exudate cell preparations, which contained an inhibitory cell, the level of accessory activity in a given population was always found to be a function of the number of dendritic cells present. Dendritic cells from all sources were nonadherent, nonphagocytic, radio- resistant, and nonspecific esterase negative. They expressed Ia antigens and lacked Fc receptors. Both epidermal and lymph node dendritic cells contain Birbeck granules, subcellular structures previously described only for Langerhans cells. Accessory activity requires viable dendritic cells but is unaffected by 1,000 rad of gamma-irradiation. However, ultraviolet irradiation abolished the activity of accessory cells. The cells that responded to periodate were IgG-negative T cells, whereas IgG-positive B cells could not be stimulated under the same conditions. Only periodate-treated T cells and dendritic cells were needed for responses to occur; removal of virtually all macrophages from these purified preparations had no effect. Dendritic cells were also required as stimulators in mixed leukocyte cultures, whereas macrophages, even though Ia positive, were inert.
Hypertriglyceridemic Very Low Density Lipoproteins Induce Triglyceride Synthesis and Accumulation in Mouse Peritoneal Macrophages
Authors: Sandra H. Gianturco, William A. Bradley, Antonio M. Gotto, Joel D. Morrisett, Duane L. Peavy
Journal: Journal of Clinical Investigation (1982)

Triglyceride-rich lipoproteins may be responsible for the lipid accumulation in macrophages that can occur in hypertriglyceridemia. Chylomicrons and very low density lipoproteins (VLDL, total and with flotation constant [Sf] 100-400) from fasting hypertriglyceridemic subjects induced a massive accumulation of oil red O-positive inclusions in unstimulated peritoneal macrophages. Cell viability was not affected. The predominant lipid that accumulated in cells exposed to hypertriglyceridemic VLDL was triglyceride. Hypertriglyceridemic VLDL stimulated the incorporation of [14C]oleate into cellular triglyceride up to ninefold in 16 h, but not into cholesteryl esters. Mass increase in cellular triglyceride was 38-fold. The stimulation of cellular triglyceride formation was dependent on time, temperature, and concentration of hypertriglyceridemic VLDL. By contrast, VLDL, low density, and high density lipoproteins from fasting normolipemic subjects had no significant effect on oleate incorporation into neutral lipids or on visible lipid accumulation.
Haploinsufficiency of Target of Rapamycin Attenuates Cardiomyopathies in Adult Zebrafish
Authors: Yonghe Ding, Xiaojing Sun, Wei Huang, Tiffany Hoage, Margaret Redfield, Sudhir Kushwaha, Sridhar Sivasubbu, Xueying Lin, Stephen Ekker, Xiaolei Xu
Journal: Circulation Research (2011)

Rationale: Although a cardioprotective function of target of rapamycin (TOR) signaling inhibition has been suggested by pharmacological studies using rapamycin, genetic evidences are still lacking. We explored adult zebrafish as a novel vertebrate model for dissecting signaling pathways in cardiomyopathy. Objective: We generated the second adult zebrafish cardiomyopathy model induced by doxorubicin. By genetically analyzing both the doxorubicin and our previous established anemia-induced cardiomyopathy models, we decipher the functions of TOR signaling in cardiomyopathies of different etiology. Methods and Results: Along the progression of both cardiomyopathy models, we detected dynamic TOR activity at different stages of pathogenesis as well as distinct effects of TOR signaling inhibition. Nevertheless, cardiac enlargement in both models can be effectively attenuated by inhibition of TOR signaling through short-term rapamycin treatment. To assess the long-term effects of TOR reduction, we used a zebrafish target of rapamycin ( ztor ) mutant identified from an insertional mutagenesis screen. We show that TOR haploinsufficiency in the ztor heterozygous fish improved cardiac function, prevented pathological remodeling events, and ultimately reduced mortality in both adult fish models of cardiomyopathy. Mechanistically, these cardioprotective effects are conveyed by the antihypertrophy, antiapoptosis, and proautophagy function of TOR signaling inhibition. Conclusions: Our results prove adult zebrafish as a conserved novel vertebrate model for human cardiomyopathies. Moreover, we provide the first genetic evidence to demonstrate a long-term cardioprotective effect of TOR signaling inhibition on at least 2 cardiomyopathies of distinct etiology, despite dynamic TOR activities during their pathogenesis.
SEROLOGICAL REACTIONS WITH A VIRUS CAUSING RABBIT PAPILLOMAS WHICH BECOME CANCEROUS
Authors: John G. Kidd, J. W. Beard, Peyton Rous
Journal: The Journal of Experimental Medicine (1936)

A method has been devised for serological tests with a virus producing rabbit papillomas that become carcinomatous. The discrete character of the growths caused by the virus when suitably diluted fits it notably for quantitative experimentation. It shows no tendency to lie latent in domestic rabbits though it does so on occasion in cottontails, the natural hosts. Sera which partially neutralize it do not alter its character, or attenuate it, but merely cut down the number of its effective entities. The serum of normal domestic rabbits is ordinarily devoid of neutralizing influence on the virus, but that of animals carrying the papillomas usually exhibits neutralizing power soon after these appear. The rate at which this power increases depends in general upon the amount of papillomatous tissue developing, but exceptions to the rule occur, the presence of fairly large growths being compatible with a lack of such powers in demonstrable amount. Even when the antiviral power is great it has no evident influence on the course of established papillomas, other factors determining whether these enlarge or retrogress. It acts to prevent successful reinoculation of the animal, however.
MicroRNA-31 Predicts the Presence of Lymph Node Metastases and Survival in Patients with Lung Adenocarcinoma
Authors: Wei Meng, Zhenqing Ye, Ri Cui, James Perry, Vaia Dedousi-Huebner, Alexander Huebner, Yao Wang, Bin Li, Stefano Volinia, Hiroshi Nakanishi, Taewan Kim, Sung-Suk Suh, Leona W. Ayers, Patrick Ross, Carlo M. Croce, Arnab Chakravarti, Victor X. Jin, Tim Lautenschlaeger
Journal: Clinical Cancer Research (2013)

We conducted genome-wide miRNA-sequencing (miRNA-seq) in primary cancer tissue from patients of lung adenocarcinoma to identify markers for the presence of lymph node metastasis.Markers for lymph node metastasis identified by sequencing were validated in a separate cohort using quantitative PCR. After additional validation in the The Cancer Genome Atlas (TCGA) dataset, functional characterization studies were conducted in vitro.MiR-31 was upregulated in lung adenocarcinoma tissues from patients with lymph node metastases compared with those without lymph node metastases. We confirmed miR-31 to be upregulated in lymph node-positive patients in a separate patient cohort (P = 0.009, t test), and to be expressed at higher levels in adenocarcinoma tissue than in matched normal adjacent lung tissues (P < 0.0001, paired t test). MiR-31 was then validated as a marker for lymph node metastasis in an external validation cohort of 233 lung adenocarcinoma cases of the TCGA (P = 0.031, t test). In vitro functional assays showed that miR-31 increases cell migration, invasion, and proliferation in an ERK1/2 signaling-dependent manner. Notably, miR-31 was a significant predictor of survival in a multivariate cox regression model even when controlling for cancer staging. Exploratory in silico analysis showed that low expression of miR-31 is associated with excellent survival for T2N0 patients.We applied miRNA-seq to study microRNomes in lung adenocarcinoma tissue samples for the first time and potentially identified a miRNA predicting the presence of lymph node metastasis and survival outcomes in patients of lung adenocarcinoma.
Normal rabbit alveolar macrophages. II. Their primary and secondary lysosomes as revealed by electron microscopy and cytochemistry.
Authors: B A Nichols
Journal: The Journal of Experimental Medicine (1976)

In this investigation, vacuoles containing tubular myelin proved to be digestive compartments with cytochemical reactivity for acid phosphatase and arylsulfatase. These cytochemical markers identify the secondary lysosomes, known to contain enzymes capable of hydrolyzing phospholipids like surfactant. Therefore, it appears that alveolar macrophages possess the enzymatic machinery for the degradation of the tubular myelin found in their digestive vacuoles. Although it thus appears evident that alveolar macrophages participate in the turnover of surfactant, the quantitative significance of this route of disposal is undetermined. This investigation has also established that acid hydrolases, so prominently displayed in the secondary lysosomes, are also localized in the rough endoplasmic reticulum and in Golgi-endoplasmic reticulum-lysosomes (GERL). Moreover, small vesicles which are produced from GERL serve as primary lysosomes in transporting digestive enzymes to the vacuoles.
Effects of Depression on Work Loss and Disability Bed Days in Individuals With Diabetes
Authors: Leonard E. Egede
Journal: Diabetes Care (2004)

Diabetes is highly prevalent in the U.S. and is associated with significant disability and increased health care costs (1–3). Depression is also highly prevalent and is a leading cause of disability, work place absenteeism, diminished or lost productivity, and increased use of health care resources (4,5). Coexisting depression occurs in 10–30% of people with diabetes, and people with diabetes have twofold increased odds of having depression compared with people without diabetes (6,7).

The objectives of this study were to determine 1 ) the effect of coexisting depression on mean work loss and disability bed days and 2 ) the effect of coexisting depression on odds of extended (defined as ≥7 days) work loss and disability bed days in individuals with and without diabetes. It was hypothesized that coexisting depression in people with diabetes would be associated with significant increases in mean disability days and odds of extended disability days.

Data from the sample adult core of 1999 National Health Interview Survey (NHIS) (8) were analyzed. The NHIS is a nationally representative household survey of U.S. adults aged ≥18 years. The sample is selected by a complex sampling design involving stratification, clustering, and multistage sampling, with a nonzero probability of selection for each person. Final weights allow estimates from the NHIS to be generalized to the adult civilian population of the U.S. (9).

Work loss …
Adrenomedullin induces vasodilation in porcine coronary conductance and resistance arteries in vivo
Authors: D. Gheorghevici, C. Zellner, J.-F. Martini, M. Nishino, A.E.M. Browne, A.Y. Guh, X. Shu, S. Zhang, B.C.K. Au, T.M. Chou, K. Sudhir, K. Chatterjee
Journal: Journal of the American College of Cardiology (1998)
Cross-presentation of Tumor Antigens Is Increased by UVC Light Tumor Treatment
Authors: Lina Matera, Stefano Garetto
Journal: Clinical Cancer Research (2009)

To the Editor: Renal carcinoma is a disease for which both positive involvement of the immune system and immunoescape mechanisms have been described. In the dendritic cell (DC) vaccine–based protocol described by Schwaab et al. ([1][1]), steps to overcome dysfunctional immune pathways have been
Meningioma mimicking features of a phaeochromocytoma.
Authors: R Gabriel, B D Harrison
Journal: BMJ (1974)

Magrath, I. T. (1974 a). International Journal of Cancer. In press. Magrath, I. T., and Ziegler, J. L. (1973). In Uganda Cancer Institute, Annual Progress Report 1972-3. Kampala, Uganda. Matsuyana, M., and Nakamura, T. (1964). Nature, 202, 200. Morrow, R. H., Pike, M. C, and Kisuule, A. (1967). British Medical Journal, 4, 323. Ngu, V. A., Burkitt, T. P., and Osunkoya, B. O. (1970). In Burkitt's Lymphoma, ed. D. P. Burkitt and D. H. Wright, p. 158. Edinburgh, Livingstone. Nora, P. F., and Preston, F. W. (1963). Surgical Climes of North America, 43, 39. Robinson, E., and Hochman, A. (1966). Journal of the National Cancer Institute, 36, 819. Skipper, H. E. (1970). In Leukaemia-Lymphoma, 14th Annual Clinical Con ference on Cancer, p. 27. Chicago, Year Book Medical Publishers. Stjemsward, ., Clifford, P., nd Svedmyer, E. (1970). In Burkitt's Lym phoma, ed. D. P. Burkitt, and D. H. Wright, p. 164. Edinburgh, Livingstone. Stjemsward, J., Jondal, M., Vanky, F., Wigzell, H., and Sealy, R. (1972). Lancet, 1, 1352. Wolff, J. A., Krivit, W., Newton, W. A., and D'Angio, G. J. (1968). New England Journal of Medicine, 279, 290. Ziegler, J. L. (1972). Cancer, 30, 1534. Ziegler, J. L. and Bluming, A. Z. (1971). British Medical Journal, 3, 508. Ziegler, J. L., Morrow, R. H., Fass, L., Kyalwazi, S. K., and Carbone, P. P. (1970). Cancer, 26, 474. Ziegler, J. L., Bluming, A. Z., Fass, L., and Morrow, R. H. (1972 a). Cancer Research, 32, 1267. Ziegler, J. L., Bluming, A. Z., Magrath, I. T., and Carbone, P. P. (1972 b). International Journal of Cancer, 10, 254.
Selective Inhibition of ADAM Metalloproteases as a Novel Approach for Modulating ErbB Pathways in Cancer
Authors: Jordan S. Fridman, Eian Caulder, Michael Hansbury, Xiangdong Liu, Genjie Yang, Qian Wang, Yvonne Lo, Bin-Bing Zhou, Maxwell Pan, Sufi M. Thomas, Jennifer R. Grandis, Jincong Zhuo, Wenqing Yao, Robert C. Newton, Steven M. Friedman, Peggy A. Scherle, Kris Vaddi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: ErbB receptor signaling pathways are important regulators of cell fate, and their dysregulation, through (epi)genetic alterations, plays an etiologic role in multiple cancers. ErbB ligands are synthesized as membrane-bound precursors that are cleaved by members of the ADAM family of zinc-dependent metalloproteases. This processing, termed ectodomain shedding, is essential for the functional activation of ErbB ligands. Recent studies suggest that elevated levels of ErbB ligands may circumvent the effectiveness of ErbB-targeted therapeutics. Here, we describe the discovery and preclinical development of potent, selective inhibitors of ErbB ligand shedding. Experimental Design: A series of biochemical and cell-based assays were established to identify selective inhibitors of ErbB ligand shedding. The therapeutic potential of these compounds was assessed in multiple in vivo models of cancer and matrix metalloprotease–related toxicity. Results: INCB3619 was identified as a representative selective, potent, orally bioavailable small-molecule inhibitor of a subset of ADAM proteases that block shedding of ErbB ligands. Administration of INCB3619 to tumor-bearing mice reduced ErbB ligand shedding in vivo and inhibited ErbB pathway signaling (e.g., phosphorylation of Akt), tumor cell proliferation, and survival. Further, INCB3619 synergized with clinically relevant cancer therapeutics and showed no overt or compounding toxicities, including fibroplasia, the dose-limiting toxicity associated with broad-spectrum matrix metalloprotease inhibitors. Conclusions: Inhibition of ErbB ligand shedding offers a potentially novel and well-tolerated therapeutic strategy for the treatment of human cancers and is currently being evaluated in the clinic.
Early Surgery Versus Conventional Treatment in Asymptomatic Very Severe Aortic Stenosis
Authors: Duk-Hyun Kang, Sung-Ji Park, Ji Hye Rim, Sung-Cheol Yun, Dae-Hee Kim, Jong-Min Song, Suk Jung Choo, Seung Woo Park, Jae-Kwan Song, Jae-Won Lee, Pyo-Won Park
Journal: Circulation (2010)

The optimal timing of surgical intervention remains controversial in asymptomatic patients with very severe aortic stenosis. We therefore compared the long-term results of early surgery and a conventional treatment strategy.From 1996 to 2006, we prospectively included a total of 197 consecutive asymptomatic patients (99 men; age, 63+/-12 years) with very severe aortic stenosis. Patients were excluded if they had angina, syncope, exertional dyspnea, ejection fraction <0.50, significant mitral valve disease, or age >85 years. Very severe aortic stenosis was defined as a critical stenosis in the aortic valve area < or =0.75 cm(2) accompanied by a peak aortic jet velocity > or =4.5 m/s or a mean transaortic pressure gradient > or =50 mm Hg on Doppler echocardiography. The primary end point was defined as the composite of operative mortality and cardiac death during follow-up. Early surgery was performed on 102 patients, and a conventional treatment strategy was used for 95 patients. There were no significant differences between the 2 groups in terms of age, gender, European System for Cardiac Operative Risk Evaluation score, or ejection fraction. During a median follow-up of 1501 days, the operated group had no operative mortalities, no cardiac deaths, and 3 noncardiac deaths; the conventional treatment group had 18 cardiac and 10 noncardiac deaths. The estimated actuarial 6-year cardiac and all-cause mortality rates were 0% and 2+/-1% in the operated group and 24+/-5% and 32+/-6% in the conventional treatment group, respectively (P<0.001), and for 57 propensity score-matched pairs, the risk of all-cause mortality was significantly lower in the operated group than in the conventional treatment group (hazard ratio, 0.135; 95% confidence interval, 0.030 to 0.597; P=0.008).Compared with the conventional treatment strategy, early surgery in patients with very severe aortic stenosis is associated with an improved long-term survival by decreasing cardiac mortality. Early surgery is therefore a therapeutic option to further improve clinical outcomes in asymptomatic patients with very severe aortic stenosis and low operative risk.
Familial microsatellite-stable non-polyposis colorectal cancer: Incidence and characteristics in a clinic-based population
Authors: V. Rovella, S. Carrara, S. Cogliandolo, A. Crucitti, C. Coco, P. Magistrelli, E. Lucci-Cordisco, M. Anti, G. Neri, M. Genuardi
Journal: Annals of Oncology (2001)
The pulmonary physician in critical care * Illustrative case 8: Acute respiratory failure following lung resection
Authors: E Beddow
Journal: Thorax (2003)

The case history of a patient who developed acute respiratory failure following lung resection is described and the incidence, clinical course, pathophysiology, and outcome following acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in surgical patients is reviewed.

A 75 year old male smoker of 60 pack-years presented with haemoptysis. Investigation revealed a bronchogenic carcinoma (non-small cell), apparently localised to the right upper lobe. The patient was otherwise well. Routine haematological and biochemical parameters were within normal limits. Spirometry was 2.4/3.01 litres (80%/76% predicted) and preoperative arterial blood gas tensions were satisfactory (Pao2 10.7 kPa, Paco2 5.6 kPa on air).

Right thoracotomy revealed extensive malignancy filling the upper lobe and involving the middle lobe at the confluence of the fissures. Histological examination confirmed bronchoalveolar carcinoma and systematic nodal dissection demonstrated N1 disease at station 11. All mediastinal nodes were clear of disease. The patient underwent uncomplicated right pneumonectomy and was extubated shortly afterwards. The morning after surgery the chest radiograph was satisfactory and gas tensions were acceptable (Pao2 13.5 kPa, Paco2 5.9 kPa using inspired oxygen concentration, Fio2 0.4). However, a repeat chest radiograph the next day revealed alveolar infiltrates in the remaining lung and, by day 3, oxygen saturations had fallen to 85% despite oxygen supplements. The alveolar shadowing progressed despite the use of diuretic and antibiotic treatment and insertion of a mini-tracheostomy. By day 4 the blood gas tensions were Pao2 6.5 kPa, Paco2 6.4 kPa (Fio2 0.21). The patient was admitted to the intensive care unit and required sedation, endotracheal intubation, and mechanical ventilation the following day.

Fibreoptic bronchoscopy and bronchoalveolar lavage were negative for microbiological staining and culture. Electrocardiograms …