tbuckley/cabot-search huggingface dataset:
A unique three-dimensional SCID-polymeric scaffold (SCID-synth-hu) model for in vivo expansion of human primary multiple myeloma cells
Authors: T Calimeri, E Battista, F Conforti, P Neri, M T Di Martino, M Rossi, U Foresta, E Piro, F Ferrara, A Amorosi, N Bahlis, K C Anderson, N Munshi, P Tagliaferri, F Causa, P Tassone
Journal: Leukemia (2011)

Multiple myeloma (MM) cells home to the bone marrow (BM) and adhere to extracellular matrix (ECM) proteins and to bone marrow stromal cells (BMSCs). The close cross talk between MM cells and cells of the non-tumor compartment within the BM has a key role in supporting tumor growth, survival and development of drug resistance. This biological scenario has led to a growing interest in novel drugs, targeting MM cells and/or interfering with their human BM milieu (HuBMM).1, 2 Based on this, appropriate in vivo models that recapitulate the complex interactions occurring between MM and its HuBMM are required for preclinical evaluation of new anti-MM agents. To date, the in vivo study of MM pathobiology and the validation of therapeutic anti-MM agents has been carried out using a variety of models of murine MM or human MM xenografts in immunocompromised mice.3 These models, however, do not replicate the HuBMM. The development of the SCID (severe combined immunodeficiency)-hu model has been an important advance, as it was the first model to recapitulate a HuBMM in mice.4, 5, 6 However, although the SCID-hu system remains a highly relevant model for preclinical investigation, it does have important limitations: (i) restricted availability of human fetal bone chips; (ii) the allogeneic nature of the fetal BM milieu versus MM cells; and (iii) the significant heterogeneity of implanted human bone chips, collected from different individuals at different gestational age, that may produce experimental variability.
Identification of Structural Determinants Supporting The Absence of IgE Cross-Reactivity Between Caprine and Bovine β-Caseins In Patients Allergic to Goat's Milk But Tolerant To Cow's Milk
Authors: S. Hazebrouck, S. Ah-Leung, E. Paty, E. Bidat, M.F. Drumare, S. Tilleul, K. Adel-Patient, J.M. Wal, H. Bernard
Journal: Journal of Allergy and Clinical Immunology (2012)
Hepatic Microvascular Regulatory Mechanisms. II. Cholinergic Mechanisms
Authors: Frank D. Reilly, Ruth V. W. Dimlich, Eugene V. Cilento, Robert S. Mccuskey
Journal: Hepatology (2007)

Several cholinergic agonists and their antagonists were administered topically at various concentrations (10−10 to 10−4 gm per ml) to the livers of anesthetized Sprague-Dawley rats. Changes in the microvasculature were measured for a period of 15 min using in vivo microscopic methods. The influence of cholinergic agonists on hepatic mast cells was determined by histochemical methods. Cholinergic agonists elicited constriction of portal venules, sinusoids, and terminal hepatic (central) venules accompanied within 5 to 20 sec by the adherence of platelets and leukocytes to the endothelial lining of these vessels. These responses were not observed in hepatic arterioles or hepatic (sublobular) venules. However, the responses drastically altered cellular flow through all segments of the microvasculature. The drugs were effective in the following ranking: bethanechol > pilocarpine > carbachol. Vascular responses were not antagonized by atropine; phentolamine modified the constrictor response of portal venules but of no other microvascular segment. These results suggest that the responses were not mediated by cholinergic (muscarinic) receptors and that the constriction of portal venules was caused by the chemical activation of a-adrenergic receptors. Histochemical methods revealed that pilocarpine and bethanechol also elicited a significant decrease in the number of visible mast cells suggestive of degranulation and the release of serotonin, histamine, and other polyanions (e.g., heparin) from these cells. Release occurred within the same period of time as the microvascular alterations (15 min). These data provide additional evidence that mast cell constituents and adrenergic mechanisms are involved in hepatic cholinergic mechanisms.
HUMAN SARCOMAS IN CULTURE
Authors: Gaetano Giraldo, Elke Beth, Yashar Hirshaut, Tadao Aoki, Lloyd J. Old, Edward A. Boyse, Harish C. Chopra
Journal: The Journal of Experimental Medicine (1971)

In a study of human sarcomas maintained in culture for periods up to two years, the following observations were made. The most prominent cell type in serially cultured osteosarcomas was fibroblastic in appearance. After 16–20 wk in culture some lines spontaneously developed foci of altered cells resembling the foci produced in monolayer cultures by oncogenic viruses. The presence of these foci in the sarcoma cultures was transient, and usually they did not reappear; but in one instance they recurred with a characteristic periodicity of several weeks. From one of the sarcoma lines, in which foci appeared after 5 months in culture, two subcultures were established from stored frozen cells and these both exhibited foci after approximately the same lapse of time. The same phenomenon has been seen with another line, suggesting that the time of appearance of foci is characteristic for particular sarcomas. Foci of similar type could sometimes be induced in monolayer cultures of human fibroblasts by filtered medium from cultured sarcomas; this bore no relation to the presence or absence of foci in the sarcoma cultures at the time the filtrate was prepared. Electron microscopy of the spontaneous and induced foci, and of the sarcoma cultures, revealed no demonstrable virus. 12 out of 15 sarcoma cultures contained an antigen (S) demonstrable by indirect immunofluorescence with human sera. It was not present in any of the original sarcoma specimens, nor in any culture lines other than sarcomas. At least 3–4 wk in culture appear to be required for its demonstration. The antigen was cytoplasmic, occurred in only a small proportion of the cells, and was unpredictably variable in its expression, even in the same culture line. It could be induced in monolayer cultures of human fibroblasts by filtrates of medium from sarcoma cultures. As with the foci, the induction of S antigen in indicator cultures was not dependent upon the expression of antigen in the sarcoma line from which the filtrates were obtained. There was no association between the presence of foci and of antigen, nor was there any apparent relation between the ability of filtrates to induce foci and their ability to induce antigen. 80% or more of the general population have S antibody, and the titer of antibody in patients with sarcoma is no higher than in normal subjects. Thus, as in the case of Burkitt's lymphoma antigen, it appears that most individuals have been exposed to S antigen. But unlike Burkitt's lymphoma, no relation has so far been established between any particular disease and a corresponding high titer or frequency of occurrence of S antibody. The occurrence of foci of altered cells and of a common antigen, and the transmission of these two characters to indicator cells by filtrates, are all suggestive of a virus specifically associated with human sarcomas, one to which the general population is widely exposed, as indicated by the prevalence of antibody.
Response to Dr Bolland's eLetter: Strontium and cardiovascular events
Authors: Jean Yves Reginster
Journal: Annals of the Rheumatic Diseases (2013)

The work carried out by the authors on calcium and the cardiovascular risk is of primary importance.1 We thank the authors for questions and comments on the Strontium ranelate Efficacy in Knee OsteoarthrItis trIAl (SEKOIA) study, safety being a primary concern for us.2

The number of emergent adverse events reported in the SEKOIA study was similar in the three treatment groups: 85.8%, 87.9% and 86.5% in the SrRan 1g, SrRan 2g and placebo groups, as well as the number of serious emergent adverse events: 17.0%, 16.5% and 17.4%, respectively. The adverse reactions …
Atrial Natriuretic Peptide Helps Prevent Late Remodeling After Left Ventricular Aneurysm Repair
Authors: Hiroshi Tsuneyoshi, Takeshi Nishina, Takuya Nomoto, Hideo Kanemitsu, Rika Kawakami, Oriyanhan Unimonh, Kazunobu Nishimura, Masashi Komeda
Journal: Circulation (2004)

Left ventricular aneurysm repair (LVR) reduces LV wall stress and improves LV function. However, as we reported previously, the initial improvement of LVR was short-term because of LV remodeling but could be maintained longer with postoperative use of an angiotensin-converting enzyme (ACE) inhibitor. Atrial natriuretic peptide (ANP) has been used to treat patients with heart failure by natriuretic and vasodilatory actions. Recent reports have suggested that ANP inhibits the rennin-angiotensin system. In this study, the effects of ANP after LVR were evaluated.Rats that had an LV aneurysm 4 weeks after left anterior descending artery ligation underwent LVR by plicating the LV aneurysm and were randomized into 2 groups: LVR+A group was intravenously administrated with 10 microg/h of carperitide, recombinant alpha-hANP, by osmotic-pump for 4 weeks, and the LVR group was given normal saline. Echocardiography revealed better LV remodeling and function in LVR+A group than in LVR group. Four weeks after LVR, left ventricular end diastolic pressure (LVEDP) and Tau were significantly lower in LVR+A group (LVEDP: 10+/-4 in LVR+A group versus 18+/-6 mm Hg in LVR group, Tau: 13+/-2 versus 17+/-2ms). End-systolic elastance (Ees) was higher in LVR+A group (Ees: 0.34+/-0.2 versus 0.19+/-0.11 mm Hg/microL). The levels of myocardial ACE activity in LVR+A group was significantly lower than in LVR group. The mRNA expressions of brain natriuretic peptide and transforming growth factor beta1 inducing fibrosis significantly decreased in LV myocardium in LVR+A group. Histologically, myocardial fibrosis was significantly reduced in LVR+A group.Intravenous administration of ANP had beneficial effects on LV remodeling, function, and fibrosis after LVR. ANP could be a useful intravenous infusion drug for postoperative management after LV repair surgery.
Prevention of Type 2 Diabetes in Subjects With Prediabetes and Metabolic Syndrome Treated With Phentermine and Topiramate Extended Release
Authors: W. Timothy Garvey, Donna H. Ryan, Robert Henry, Nancy J.V. Bohannon, Hermann Toplak, Michael Schwiers, Barbara Troupin, Wesley W. Day
Journal: Diabetes Care (2013)

OBJECTIVE To evaluate over 108 weeks the effect of phentermine and topiramate extended release (PHEN/TPM ER) treatment on progression to type 2 diabetes and/or cardiometabolic disease in subjects with prediabetes and/or metabolic syndrome (MetS) at baseline. RESEARCH DESIGN AND METHODS Subanalysis of a phase 3, randomized, placebo-controlled, double-blind study of overweight/obese subjects (BMI ≥27 to ≤45 kg/m2) with two or more comorbidities. Subjects were randomized to placebo, PHEN 7.5 mg/TPM ER 46 mg (7.5/46), or PHEN 15 mg/TPM ER 92 mg (15/92) plus lifestyle modifications for 108 weeks. Percent weight loss in the intent-to-treat population using multiple imputation (ITT-MI), annualized incidence rate of progression to type 2 diabetes, and changes in glycemia, lipid parameters, blood pressure, and waist circumference were evaluated. RESULTS At baseline, 475 subjects met the criteria for prediabetes and/or MetS. After 108 weeks, subjects with prediabetes and/or MetS in the placebo, 7.5/46, and 15/92 groups experienced mean percent weight loss of 2.5, 10.9, and 12.1%, respectively (ITT-MI; P &amp;lt; 0.0001 vs. placebo), associated with reductions of 70.5 and 78.7% in the annualized incidence rate of type 2 diabetes for those receiving 7.5/46 and 15/92, respectively (ITT, P &amp;lt; 0.05), versus placebo. The ability of PHEN/TPM ER to prevent diabetes was related to degree of weight lost and was accompanied by significant improvements in cardiometabolic parameters. PHEN/TPM ER was well tolerated by this subgroup over 2 years. CONCLUSIONS PHEN/TPM ER plus lifestyle modification produced significant weight loss and markedly reduced progression to type 2 diabetes in overweight/obese patients with prediabetes and/or MetS, accompanied by improvements in multiple cardiometabolic disease risk factors.
Cigarette smoking and irreversible airways obstruction in the West Indies
Authors: G. J. Miller
Journal: Thorax (1974)

<b>Miller, G. J. (1974).</b><i>Thorax</i>, 495-504. <b>Cigarette smoking and irreversible airways obstruction in the West Indies.</b> Two communities, one in Jamaica and one in Guyana, have been surveyed in order to investigate the relationships between cigarette smoking, respiratory symptoms, and lung function in the West Indies. Cigarette consumption was less than that reported in the United Kingdom, particularly among women. Smoking was associated with cough, phlegm, increases in total lung capacity and residual volume, and reductions in FEV%, transfer coefficient (Kco), and alveolar capillary blood volume (Vc). Vital capacity (VC) and the diffusion capacity of the alveolar membrane (Dm) were normal. After allowing for differences in age and tobacco consumption, less cough, phlegm, and airways obstruction occurred in the West Indies than has been reported in the United Kingdom. Forty-seven patients in Jamaica with chronic obstructive lung disease were followed for three years. All except six female asthmatics were either current smokers or ex-smokers. Smoking in patients was associated with a similar but more severe pattern of lung disease to that found in survey subjects with, in addition, reductions in VC and Dm. In the non-smoking asthmatics Kco, Dm, and Vc were normal. The lung function of these 47 patients was similar to that reported for UK patients even though both chronic bronchitis and hypercapnia were considerably less common in Jamaica. Emphysema was present in all six patients who died and came to necropsy. It is suggested that in the West Indies emphysema contributes more than bronchitis to airways obstruction in smokers. There was also evidence that subjects of African origin were less susceptible to the emphysema-producing effect of cigarettes than were other ethnic groups.
Advances in Treating Metastatic Bone Cancer: Summary Statement for the First Cambridge Conference
Authors: Allan Lipton, James R. Berenson, Jean-Jacques Body, Brendan F. Boyce, Oyvind S. Bruland, Michael A. Carducci, Charles S. Cleeland, Denis R. Clohisy, Robert E. Coleman, Richard J. Cook, Theresa A. Guise, Roger N. Pearse, Trevor J. Powles, Michael J. Rogers, G. David Roodman, Matthew R. Smith, Larry J. Suva, Robert L. Vessella, Katherine N. Weilbaecher, Laura King
Journal: Clinical Cancer Research (2006)

Abstract The First Cambridge Conference on Advances in Treating Metastatic Bone Cancer, a symposium held in Cambridge, Massachusetts, October 28 to 29, 2005, was convened to discuss recent advances and research related to the natural history of bone metastases and skeletal complications, bone cancer biology, treatment of myeloma and other solid tumors, and treatment-induced bone loss. The conference format combined brief presentations with extended periods of discussion. The conclusions reached during the 2-day meeting are summarized in this article and presented in more detail in the individual articles and accompanying discussion sessions that comprise the conference proceedings.
Combination chemotherapy with navelbine and continuous infusion of 5-fluorouracil in metastatic, chemotherapy refractory breast cancer
Authors: D Lombardi, M D Magri, D Crivellari, S Spazzapan, C Paolello, M De Cicco, V Di Lauro, C Scuderi, A Veronesi
Journal: Annals of Oncology (2000)
Determinants of Adaptive Evolution at the Molecular Level: the Extended Complexity Hypothesis
Authors: S. Aris-Brosou
Journal: Molecular Biology and Evolution (2004)

To explain why informational genes (i.e., those involved in transcription, translation, and related processes) are less likely than housekeeping genes to be horizontally transferred, Jain and coworkers proposed the complexity hypothesis. The underlying idea is that informational genes belong to large, complex systems of coevolving genes. Consequently, the likelihood of the successful horizontal transfer of a single gene from such an integrated system is expected to be low. Here, this hypothesis is extended to explain some of the determinants of the mode of evolution of coding sequences. It is proposed that genes belonging to complex systems are relatively less likely to be under adaptive evolution. To evaluate this "extended complexity hypothesis," 2,428 families and protein domains were analyzed. This analysis found that genes whose products are highly connected, located in intracellular components, and involved in complex processes and functions were more conserved and less likely to be under adaptive evolution than are other gene products. The extended complexity hypothesis suggests that both the mode and the rate of evolution of a protein are influenced by its gene ontology (localization, biological process, and molecular function) and by its connectivity.
Decreased Expression of miR216a Contributes to Non–Small-Cell Lung Cancer Progression
Authors: Ren-Tao Wang, Meng Xu, Cheng-Xiong Xu, Zhi-Gang Song, Hua Jin
Journal: Clinical Cancer Research (2014)

The aim of the present study is to investigate the role and mechanism of miR216a in non-small-cell lung cancer (NSCLC).The expression of miR216a in NSCLC cell lines and from NSCLC patient specimens was measured by real-time qRT-PCR. The correlation between gene expression and patient survival was analyzed using Kaplan-Meier methods. The effects of miR216a on NSCLC cell growth and metastasis were examined both in vitro and in vivo by overexpressing or inhibiting miR216a. Finally, the effect of miR216a on chemoresistance was investigated by MTT assay and flow cytometry.miR216a expression was downregulated in specimens from patients with NSCLC compared with corresponding nontumor lung tissues. Clinical data indicate that decreased miR216a expression is inversely correlated with cancer stage, metastasis, and poor survival in patients with NSCLC. Our data also show that overexpression of miR216a suppresses NSCLC cell growth and metastasis, and enhances cisplatin-induced cell growth inhibition and apoptosis. In contrast, inhibition of miR216a stimulates NSCLC cell growth and metastasis, and suppresses cisplatin-induced cell growth inhibition and apoptosis. Furthermore, we demonstrate that miR216a exerts its role by directly targeting eIF4B and ZEB1.Our findings suggest that miR216a is a cancer suppressor miRNA and that overexpression of miR216a is a novel NSCLC treatment strategy. In addition, our clinical data indicate that miR216a may be a useful biomarker for predicting NSCLC progression.
The comparison of clinical features between JAK2<sup>V617F</sup> positive and negative subgroups of essential thrombocythemia
Authors: S. Zhang, J. Li, M. Lu
Journal: Journal of Clinical Oncology (2007)

17523 Background: JAK2 V617F is a novel molecular mechanisms of BCR/ABL-negative MPD especially polycythemia vera. However, its role may not be clearly identified in essential thrombocythemia (ET). Methods: To investigate its prevalence and clinical significance in Chinese ET patients, Allele-Specific PCR (AS-PCR) in combination with sequence analysis were introduced to screen JAK2 V617F mutation in our research. Genomic DNA of 40 ET patients was extracted from peripheral blood mononuclear cells, and AS-PCR was firstly adopted to amplify the exon 12 of JAK2 gene which harbored V617F mutation. The positive samples with JAK2 V617F mutation were further confirmed by sequence analysis. In addition, the features of JAK2 V617F positive and negative subgroup were compared according to laboratory examination. Results: The JAK2 V617F mutation was identified in 18 ET patients (45%, 18/40) by AS-PCR and sequence analysis. Its presence is significantly associated with a higher hemoglobin, hematocrit and neutrophilic granulocyte percentage in ET patients. Conclusions: AS-PCR is a sensitive and accurate technique in identification of JAK2 V617F mutation. JAK2 V617F mutation is of important significance in Chinese ET patients. Moreover, this ET subgroup may be prone to transform to polycythemia vera. No significant financial relationships to disclose.
Differences in Tumor Regulatory T-Cell Localization and Activation Status Impact Patient Outcome
Authors: Christine Ménétrier-Caux, Michael Gobert, Christophe Caux
Journal: Cancer Research (2009)

The presence of regulatory T cells (Treg) has been described in a large panel of solid tumors. However, their impact on tumor progression differs according to the tumor type analyzed. We recently obtained evidence in breast carcinoma that Treg localized within lymphoid aggregates, but not in the tumor bed, have a negative impact on patients' survival. Moreover, we showed selective Treg recruitment through CCR4/CCL22 in the lymphoid aggregates upon contact with dendritic cells (DC), where they became strongly and selectively activated (ICOS(high)) and block conventional T-cell response. Here, we discuss the meaning and potential implication of these novel findings.
Complement Factor H Limits Immune Complex Deposition and Prevents Inflammation and Scarring in Glomeruli of Mice with Chronic Serum Sickness
Authors: Jessy J. Alexander, Matthew C. Pickering, Mark Haas, Iyabo Osawe, Richard J. Quigg
Journal: Journal of the American Society of Nephrology (2004)

Factor H is the major complement regulator in plasma. Abnormalities in factor H have been implicated in membranoproliferative glomerulonephritis in both humans and experimental animals. It has been shown that factor H on rodent platelets functions analogously to human erythrocyte complement receptor 1 in its role to traffic immune complexes to the mononuclear phagocyte system. C57BL/6 factor H-deficient mice (Cfh−/−) and wild-type (wt) controls were immunized daily for 5 wk with heterologous apoferritin to study the chronic serum sickness GN model. Immunizations were started in 6- to 8-wk-old mice, which was before the development of spontaneous membranoproliferative glomerulonephritis in some Cfh−/− animals. Glomerular deposition of IgG immune complexes in glomeruli was qualitatively and quantitatively increased in Cfh−/− mice compared with wt mice. Consistent with the increase in glomerular immune complexes and possibly because of alternative pathway complement activation, Cfh−/− mice had increased glomerular C3 deposition. Wt mice developed no glomerular pathology. In contrast, Cfh−/− mice developed diffuse proliferative GN with focal crescents and glomerulosclerosis. In addition, there was significantly increased expression of collagen IV, fibronectin, and laminin mRNA in Cfh−/− glomeruli. These data show a role for platelet-associated factor H to process immune complexes and limit their accumulation in glomeruli. Once deposited in glomeruli, excessive complement activation can lead to glomerular inflammation and the rapid development of a scarring phenotype.