tbuckley/cabot-search huggingface dataset:
Tumor-Host Interactions: A Far-Reaching Relationship
Authors: Sandra S. McAllister, Robert A. Weinberg
Journal: Journal of Clinical Oncology (2010)

Carcinomas are composed of neoplastic epithelial cells, which form the heart of the tumor, as well as a variety of mesenchymal cell types and extracellular matrix components that comprise the tumor stroma, often termed its microenvironment. The normal counterparts of some stromal cells are thought to limit tumor growth, while tumor-associated stromal cells have been convincingly shown to actively promote tumor progression via complex heterotypic interactions with the nearby carcinoma cells. More recent advances have revealed that tumor-host interactions extend well beyond the local tissue microenvironment (ie, interactions between the neoplastic cells and the nearby stroma) and that tumors not only respond to, but actively perturb host organs at distant anatomic sites. This indicates that many aspects of tumor biology can only be explained by a detailed understanding of both local and systemic interactions, yet we currently have only a fragmentary understanding of both processes. In this review, we address the recent advances in our understanding of the contributions of local and systemic environments to cancer progression, the ability of tumors to actively perturb the host environment, and current therapeutic approaches that are designed to disrupt tumor-host relationships.
Acute Infective Polyneuritis
Authors: C. P. Petch
Journal: BMJ (1945)

MEDICAL 10URALsteadily; in two weeks foot-drop disappeared.After three weeks fine movements of hands became possible and anaesthesia was absent.Patient was discharged after six weeks; shortly beforehand paraesthesiae had gone, but although power greatly improved, it would not permit severe exertion. Severe CasesOf the series only three cases became bed-ridden; one of these is described.Case 12.-Gave a history of jungle sores beginning two months previously; finally healed a few days before admission.Present complaints: tingling of extremities, unsteadiness of gait, and blurring of vision.These occurred at approximately the same time as the sores healed.On examination, general condition good.No evidence of avitaminosis or anaemia.Scars of healed jungle sores on legs and forearms.All systems normal except C.N.S. C.N.S. examinationi: pupils and cranial nerves normal; weakness of grip- L. > R.; slight weakness of extensors of wrist and dorsiflexors of ankle; no anaesthesia; upper-liffib tendon reflexes present; ankle- and knee-jerks absent on both sides.Two days after admission:- Tendency to foot-drop, L.>R.; impairment of all forms of sensation up to knees; astereognosis present; biceps jerks now absent.There followed a rapid increase in weakness, maximal peripherally and spreading towards the trunk.Ten days after admission:-
The role of membrane lipids in the survival of red cells in hereditary spherocytosis
Authors: R. A. Cooper, J. H. Jandl
Journal: Journal of Clinical Investigation (1969)

Red cells in hereditary spherocytosis (HS) have a decreased ratio of membrane surface area to cell volume and therefore a spheroidal shape. This abnormality in shape predisposes them to pooling and destruction in the spleen. Although splenectomy prevents hemolysis in HS, the red cell defect, as manifested by spheroidicity, increased autohemolysis, excesive permeability to sodium, and hypermetabolism, persists. The role of membrane lipids in these manifestations in vitro and in cell survival in vivo was examined.
Inhaled corticosteroids and growth of airway function in asthmatic children
Authors: P.J.F.M. Merkus, W. van Pelt, J.C. van Houwelingen, L.E.M. van Essen-Zandvliet, E.J. Duiverman, K.F. Kerrebijn, P.H. Quanjer
Journal: European Respiratory Journal (2004)

Airway inflammation and remodelling play an important role in the pathophysiology of asthma. Remodelling may affect childhood lung function, and this process may be reversed by anti-inflammatory treatment. The current study assessed longitudinally whether asthma affects growth of airway function relative to airspaces, and if so whether this is redressed by inhaled corticosteroids (ICS). Every 4 months for up to 3 yrs, lung function was assessed in 54 asthmatic children (initial age 7–16 yrs), who inhaled 0.2 mg salbutamol <i>t.i.d.</i> and 0.2 mg budesonide <i>t.i.d.</i> (β<sub>2</sub>‐agonist (BA)+ICS), or placebo (PL) <i>t.i.d</i>. (BA+PL) in a randomised, double-blind design. Measurements were carried out before and after maximal bronchodilation. Airway growth was assessed from the change of forced expiratory volume in one second and of maximal expiratory flows (at 60% and 40% of total lung capacity (TLC) remaining in the lung) relative to TLC, as measures of more central, intermediate and more peripheral airways. Growth patterns were compared with the longitudinal findings in 376 healthy children. Airway patency after maximal bronchodilation in patients on BA+PL remained reduced compared to healthy subjects, whereas in patients on BA+ICS a marked improvement was observed to subnormal. No differences between patients and controls could be demonstrated for growth patterns of central and intermediate airway function. Compliance with BA+ICS was 75% of the prescribed dose, resulting in significant, sustained improvement of symptoms and postbronchodilator calibre of central and intermediate airways to subnormal within 2 months, but postbronchodilator small airway patency remained reduced, though improved compared to patients on BA+PL. Anti-inflammatory treatment of asthmatic children is associated with normal functional development of central and intermediate airways. The persistently reduced postbronchodilator patency of peripheral airways may reflect remodelling, or insufficient anti-inflammatory treatment.
1155 PRIMARY HUMAN HEPATOCYTES AND CLINICAL STRAINS OF HEPATITIS C VIRUS: A HIGHLY RELEVANT IN VITRO MODEL FOR ANTIVIRAL DRUG DEVELOPMENT
Authors: C. Gondeau, P. Briolotti, P.-A. Rubbo, M.-P. Ripault, J.-M. Fabre, J. Ramos, P. Maurel, D. Larrey, M. Daujat-Chavanieu
Journal: Journal of Hepatology (2013)
Respiratory diseases in pregnancy bullet 4: Women with cystic fibrosis and their potential for reproduction
Authors: F P Edenborough
Journal: Thorax (2001)

While it has long been appreciated that up to 98% of men with cystic fibrosis (CF) are infertile due to a failure to develop, or early blockage of, the mesonephric ducts and vas deferens,1 the effect of CF on the fertility of women is less clear. Survival is now into the fourth decade of life and, with the largest growth in the CF population seen in the adult age groups,2 it is not surprising that the issues of fertility and reproduction are increasingly raised in adult clinics. Pregnancy is possible and increasing numbers of children are born to women with CF each year.3 Since the first pregnancy in 1960,4 management of all aspects of CF has improved and so the prognosis for mother and child has also improved. This paper reviews the pathophysiology of CF in the female reproductive tract, its effect on fertility and the ability to carry a pregnancy, and the outcome for mother and infant.

CF is an autosomal recessive disease arising from abnormalities on the long arm of chromosome 7. Defective production of the cystic fibrosis transmembrane conductance regulator (CFTR) protein5—a complex channel regulating the passage of chloride and, indirectly, sodium and water across luminal cell membranes—results in thickened and desiccated secretions throughout the respiratory and alimentary tracts, sweat ducts, and the reproductive organs. The principal manifestations in adults are due to undernutrition resulting from pancreatic insufficiency and malabsorption, and respiratory failure due to chronic infection, bronchiectasis, and progressive lung destruction. Diabetes mellitus and cirrhosis are secondary manifestations resulting from pancreatic and biliary damage and are increasingly seen in older patients.

CFTR is found in large quantities on the cervix6 and, although anatomically normal, histologically the columnar epithelium is distorted by mucus filled balloon or cygnet ring cells. The …
Multiple Choices
Authors: Martin Prlic, Leo Lefrancois, Stephen C. Jameson
Journal: The Journal of Experimental Medicine (2002)

The generation of memory T cells in immune responses has been extensively studied over recent years, yet the requirements for production and persistence of a functional memory pool are still unclear. For example, while there is compelling evidence that survival of memory cells does not require TCR–MHC engagements (1, 2), recent evidence indicates that such interactions may be needed to maintain functional activity of these cells (3, 4). Furthermore, there is growing evidence that cytokines play a major role in deciding the fate of CD8 memory cells, although the precise mechanisms by which these effects are mediated remain unknown.
Effect of Oral Chenodeoxycholic Acid on Bile Acid Kinetics and Biliary Lipid Composition in Women with Cholelithiasis
Authors: Rudy G. Danzinger, Alan F. Hofmann, Johnson L. Thistle, Leslie J. Schoenfield
Journal: Journal of Clinical Investigation (1973)

Bile acid kinetics and biliary lipid composition were characterized in six women with gallstones before and after 6 mo of oral therapy with chenodeoxycholic acid, an agent that induces dissolution of cholesterol gallstones in man. Over a dosage range of 1-4 g/day, absorption varied from 0.8 to 2.3 g/day. The chenodeoxycholic acid pool expanded two-to sixfold, and bile became composed predominantly (> 90%) of chenodeoxycholic acid conjugated chiefly with glycine. Cholic acid and deoxycholic acid pools decreased markedly, so that the total bile acid pool expanded much less, about twofold on the average. Cholic acid synthesis decreased in five of the six patients, consistent with negative feedback inhibition of cholic acid synthesis by chenodeoxycholic acid. In four patients whose bile was above or close to saturation with cholesterol, the bile became unsaturated; in two patients, whose bile was unsaturated, it remained so. In five patients with radiolucent gallstones, chenodeoxycholic acid therapy was continued after completion of kinetic and composition measurements; the stones decreased in size or dissolved entirely during the subsequent 6 to 18 mo. Similar measurements of bile acid kinetics and biliary lipid composition were made before and after a 6-mo period without medication in a control group of six healthy women; no changes occurred.
Aerobic walking or strengthening exercise for osteoarthritis of the knee? A systematic review
Authors: E Roddy
Journal: Annals of the Rheumatic Diseases (2005)

To compare the efficacy of aerobic walking and home based quadriceps strengthening exercises in patients with knee osteoarthritis.The Medline, Pubmed, EMBASE, CINAHL, and PEDro databases and the Cochrane controlled trials register were searched for randomised controlled trials (RCTs) of subjects with knee osteoarthritis comparing aerobic walking or home based quadriceps strengthening exercise with a non-exercise control group. Methodological quality of retrieved RCTs was assessed. Outcome data were abstracted for pain and self reported disability and the effect size calculated for each outcome. RCTs were grouped according to exercise mode and the data pooled using both fixed and random effects models.35 RCTs were identified, 13 of which met inclusion criteria and provided data suitable for further analysis. Pooled effect sizes for pain were 0.52 for aerobic walking and 0.39 for quadriceps strengthening. For self reported disability, pooled effect sizes were 0.46 for aerobic walking and 0.32 for quadriceps strengthening.Both aerobic walking and home based quadriceps strengthening exercise reduce pain and disability from knee osteoarthritis but no difference between them was found on indirect comparison.
mTOR Is a Promising Therapeutic Target Both in Cisplatin-Sensitive and Cisplatin-Resistant Clear Cell Carcinoma of the Ovary
Authors: Seiji Mabuchi, Chiaki Kawase, Deborah A. Altomare, Kenichirou Morishige, Kenjiro Sawada, Masami Hayashi, Masahiko Tsujimoto, Mareo Yamoto, Andres J. Klein-Szanto, Russell J. Schilder, Masahide Ohmichi, Joseph R. Testa, Tadashi Kimura
Journal: Clinical Cancer Research (2009)

Mammalian target of rapamycin (mTOR) plays a central role in cell proliferation and is regarded as a promising target in cancer therapy, including for ovarian cancer. This study aimed to examine the role of mTOR as a therapeutic target in clear cell carcinoma of the ovary, which is regarded as an aggressive, chemoresistant histologic subtype.Using tissue microarrays of 98 primary ovarian cancers (52 clear cell carcinomas and 46 serous adenocarcinomas), the expression of phospho-mTOR was assessed by immunohistochemistry. Then, the growth-inhibitory effect of mTOR inhibition by RAD001 (everolimus) was examined using two pairs of cisplatin-sensitive parental (RMG1 and KOC7C) and cisplatin-resistant human clear cell carcinoma cell lines (RMG1-CR and KOC7C-CR) both in vitro and in vivo.Immunohistochemical analysis showed that mTOR was more frequently activated in clear cell carcinomas than in serous adenocarcinomas (86.6% versus 50%). Treatment with RAD001 markedly inhibited the growth of both RMG1 and KOC7C cells both in vitro and in vivo. Increased expression of phospho-mTOR was observed in cisplatin-resistant RMG1-CR and KOC7C-CR cells, compared with the respective parental cells. This increased expression of phospho-mTOR in cisplatin-resistant cells was associated with increased activation of AKT. RMG1-CR and KOC7C-CR cells showed greater sensitivity to RAD001 than did parental RMG1 and KOC7C cells, respectively, in vitro and in vivo.mTOR is frequently activated in clear cell carcinoma and can be a promising therapeutic target in the management of clear cell carcinoma. Moreover, mTOR inhibition by RAD001 may be efficacious as a second-line treatment of recurrent disease in patients previously treated with cisplatin.
Matrix Metalloproteinase-7 Affects Connexin-43 Levels, Electrical Conduction, and Survival After Myocardial Infarction
Authors: Merry L. Lindsey, G. Patricia Escobar, Rupak Mukherjee, Danielle K. Goshorn, Nina J. Sheats, James A. Bruce, I. Matthew Mains, Jennifer K. Hendrick, Kenneth W. Hewett, Robert G. Gourdie, Lynn M. Matrisian, Francis G. Spinale
Journal: Circulation (2006)

Background— Matrix metalloproteinases (MMPs) contribute to left ventricular remodeling after myocardial infarction (MI). Specific causative roles of particular MMPs, however, remain unclear. MMP-7 is abundant in cardiomyocytes and macrophages, but MMP-7 function after MI has not been defined. Methods and Results— Wild-type (WT; n=55) and MMP-7–null (MMP-7 −/− ; n=32) mice underwent permanent coronary artery ligation for 7 days. MI sizes were similar, but survival was greatly improved in MMP-7 −/− mice. The survival difference could not be attributed to differences in left ventricular dilation because end-diastolic volumes increased similarly. ECG analysis revealed a prolonged PR interval in WT but not in MMP-7 −/− post-MI mice. Post-MI conduction velocity, determined by optically mapping electrical wavefront propagation, decreased to 78±6% of control for WT and was normalized in MMP-7 −/− mice. In WT mice, slower conduction velocity correlated with a 53% reduction in the gap junction protein connexin-43. Direct binding of MMP-7 to connexin-43, determined by surface plasmon resonance technology, occurred in a dose-dependent manner. Connexin-43 processing by MMP-7 was confirmed by in silico and in vitro substrate analyses and MMP-7 infusion induced arrhythmias in vivo. Conclusions— MMP-7 deletion results in improved survival and myocardial conduction patterns after MI. This is the first report to implicate MMP-7 in post-MI remodeling and to demonstrate that connexin-43 is a novel MMP-7 substrate.
Lipoprotein oxidation in cardiovascular disease: chief culprit or innocent bystander?
Authors: Jay W. Heinecke
Journal: The Journal of Experimental Medicine (2006)

Oxidation of low-density lipoprotein (LDL) is thought to contribute to atherosclerosis and cardiovascular disease. Consistent with this idea, the antioxidant drug probucol reduces the risk of restenosis, a form of cardiovascular disease, in humans. However, a new study now suggests that the protective effect of probucol depends not on its ability to inhibit lipid oxidation, but on its ability to induce the stress-induced antiinflammatory enzyme heme oxygenase (HO)-1. This might explain why other antioxidants, such as vitamin E, fail to prevent cardiovascular disease in humans.
Efficacy and tolerability of anti‐immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR
Authors: A. M. Vignola, M. Humbert, J. Bousquet, L‐P. Boulet, S. Hedgecock, M. Blogg, H. Fox, K. Surrey
Journal: Allergy (2004)

Background: Anti‐IgE therapy could be particularly beneficial for patients with concomitant disease as it targets a common factor in both diseases. The aim of this study was to evaluate the efficacy and safety of omalizumab in patients with concomitant moderate‐to‐severe asthma and persistent allergic rhinitis. Methods: This multicentre, randomized, double‐blind, parallel‐group, placebo‐controlled trial evaluated the safety and efficacy of omalizumab. A total of 405 patients (12–74 years) with a stable treatment (≥ 400 μ g budesonide Turbuhaler ® ) and ≥ 2 unscheduled medical visits for asthma during the past year or ≥ 3 during the past 2 years were enrolled. Patients received omalizumab (≥ 0.016 mg/kg/IgE [IU/ml] per 4 weeks) or placebo for 28 weeks. Results: Fewer patients treated with omalizumab experienced asthma exacerbations (20.6%) than placebo‐treated patients (30.1%), P = 0.02. A clinically significant (≥ 1.0 point) improvement in both Asthma Quality of Life Questionnaire and Rhinitis Quality of Life Questionnaire occurred in 57.7% of omalizumab patients compared with 40.6% of placebo patients ( P &lt; 0.001). Omalizumab reduced Wasserfallen symptom scores for asthma ( P = 0.023), rhinitis ( P &lt; 0.001) and the composite asthma/rhinitis scores ( P &lt; 0.001) compared with placebo. Serious adverse events were observed in 1.4% of omalizumab‐treated patients and 1.5% of placebo‐treated patients. Conclusion: Omalizumab is well tolerated and effective in preventing asthma exacerbations and improving quality of life in patients with concomitant asthma and persistent allergic rhinitis.
Gray zone lymphoma with features intermediate between classical<scp>H</scp>odgkin lymphoma and diffuse large<scp>B</scp>‐cell lymphoma:<scp>C</scp>haracteristics, outcomes, and prognostication among a large multicenter cohort
Authors: Andrew M. Evens, Jennifer A. Kanakry, Laurie H. Sehn, Athena Kritharis, Tatyana Feldman, Aimee Kroll, Randy D. Gascoyne, Jeremy S. Abramson, Adam M. Petrich, Francisco J. Hernandez‐Ilizaliturri, Zeina Al‐Mansour, Camille Adeimy, Jessica Hemminger, Nancy L. Bartlett, Anthony Mato, Paolo F. Caimi, Ranjana H. Advani, Andreas K. Klein, Chadi Nabhan, Sonali M. Smith, Jesus C. Fabregas, Izidore S. Lossos, Oliver W. Press, Timothy S. Fenske, Jonathan W. Friedberg, Julie M. Vose, Kristie A. Blum
Journal: American Journal of Hematology (2015)

Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B‐cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty‐three percent of patients presented with MGZL, whereas 57% had non‐MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P = 0.0001); more often had bone marrow involvement (19% versus 0%, P = 0.001); &gt;1 extranodal site (27% versus 8%, P = 0.014); and advanced stage disease (81% versus 13%, P = 0.0001); but they had less bulk (8% versus 44%, P = 0.0001), compared with MGZL patients. Common frontline treatments were cyclophosphamide‐doxorubicin‐vincristine‐prednisone +/− rituximab (CHOP+/−R) 46%, doxorubicin‐bleomycin‐vinblastine‐dacarbazine +/− rituximab (ABVD+/−R) 30%, and dose‐adjusted etoposide‐doxorubicin‐cyclophosphamide‐vincristine‐prednisone‐rituximab (DA‐EPOCH‐R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31‐month median follow‐up, 2‐year progression‐free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. Additionally, patients treated with ABVD+/−R had markedly inferior 2‐year PFS (22% versus 52%, P = 0.03) compared with DLBCL‐directed therapy (CHOP+/−R and DA‐EPOCH‐R), which persisted on Cox regression (hazard ratio, 1.88; 95% confidence interval, 1.03–3.83; P = 0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18–0.69; P = 0.002). Collectively, GZL is a heterogeneous and likely more common entity and often with nonmediastinal presentation, whereas outcomes seem superior when treated with a rituximab‐based, DLBCL‐specific regimen. Am. J. Hematol. 90:778–783, 2015. © 2015 Wiley Periodicals, Inc.
Prolonged hypoparathyroidism presenting eventually as second trimester abortion.
Authors: R Eastell, C J Edmonds, R C de Chayal, I R McFadyen
Journal: BMJ (1985)

Street.They appeared on challenge to be sensitive to different foods, but tartrazine and benzoic acid were top of the list. ArthritisGouty arthritis is aggravated by alcohol and by high purine and high protein diets.Although most patients with rheumatoid arthritis do not respond to food exclusions or challenges, a patient was reported from the Hammersmith Hospital whose arthritis was clearly shown to be aggravated by milk and cheese.
Multivitamins for Cancer Prevention in Men—Reply
Authors: J. Michael Gaziano, Howard D. Sesso
Journal: JAMA (2013)

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Renal Carcinoma Associated With Succinate Dehydrogenase B Mutation: A New and Unique Subtype of Renal Carcinoma
Authors: Julie Y. Paik, Christopher W. Toon, Diana E. Benn, Hilda High, Csilla Hasovitz, Nick Pavlakis, Roderick J. Clifton-Bligh, Anthony J. Gill
Journal: Journal of Clinical Oncology (2014)