tbuckley/cabot-search huggingface dataset:
THE COMPLEMENT-DEPENDENT BACTERIOLYTIC ACTIVITY OF NORMAL HUMAN SERUM
Authors: Alastair C. Wardlaw
Journal: The Journal of Experimental Medicine (1962)

The bacteriolytic activity of normal human serum on a rough strain of E. coli has been studied by a turbidimetric method. Bacteriolysis was found to be markedly dependent on ionic strength and pH, with optima at micro = 0.06 and pH 8.3-8.5, respectively. The method of cultivating the cells also influenced the rapidity of lysis. Lysis was temperature-dependent and was exhibited by all samples of human serum tested. Microscopically, organisms incubated with serum were observed to swell, loose their rod shape and eventually burst, leaving remnants of the cell membrane in suspension. Sphaeroplasts were obtained by brief exposure of cells to serum followed by dilution into 5 per cent sucrose. The bacteriolytic reaction was shown to require complement. No definite requirement for properdin or specific antibody in this system could be demonstrated by the absorption of serum with zymosan and with homologous cells respectively. The latter procedure was found to reduce bacteriolytic activity by removal of serum lysozyme. Absorption of serum with bentonite also led to loss of bacteriolytic activity which could be restored with lysozyme. The organism was not lysed by lysozyme alone, but lysis occurred with lysozyme + EDTA in tris buffer. The possibility of complement acting independently of antibody or properdin, in certain instances, is discussed in relation to bacterial cell wall structure. Data are presented supporting the hypothesis that the "substrate" of complement in cell membranes is a lipid or lipoprotein.
RAPID LYMPHOCYTE RECOGNITION OF HISTOINCOMPATIBILITY
Authors: J. Andersson, D. Killander, E. Möller, G. Möller
Journal: The Journal of Experimental Medicine (1970)

The mechanism of growth stimulation in allogeneic lymphocytes mixed in vitro was studied at the cell level by means of cytophotometric techniques. A pronounced increase in fluorescence intensity of fixed and acridine orange (AO) stained lymphocytes was observed as soon as after 1–3 hr in mixed culture. No increase in the amount of DNA took place during this time. The higher fluorescence intensity was due to an increased accessibility of AO binding sites in the deoxyribonucleoprotein (DNP) complex, most probably as a result of weakened bonds between the DNA and the protein moiety in the DNP complex. Similar DNP changes have been found in other systems of growth stimulation and may be one prerequisite for later induction of cellular synthetic processes. Increased AO binding only occurred when the lymphocyte donors were incompatible at the major histocompatibility locus (HL-A); there was no change in AO binding in cases of HL-A identity. The AO binding reaction probably reflects a specific recognition of HL-A antigens, whereas other antigenic discrepancies between the individuals do not seem to cause an analogous response.
Role of Mineralocorticoid Receptor Antagonists in Cardiovascular Disease
Authors: Carlos M. Ferrario, Ernesto L. Schiffrin
Journal: Circulation Research (2014)

Aldosterone exerts its best known sodium homeostasis actions by controlling sodium excretion at the level of the distal tubules via activation of the apical epithelial sodium channel and the basolateral Na(+)/K(+)ATPase pump. Recently, this mineralocorticoid hormone has been demonstrated to act on the heart and blood vessels. Excess release of aldosterone in relation to the salt status induces both genomic and nongenomic effects that by promoting endothelial dysfunction, and vascular and cardiorenal adverse remodeling, contribute to the target organ damage found in hypertension, heart failure, myocardial infarction, and chronic renal failure. Mineralocorticoid receptor blockers have been shown to be highly effective in resistant hypertension and to slow down heart failure progression, and in experimental animals, the development of atherosclerosis. Blockade of the action of aldosterone and potentially other mineralocorticoid steroids has been increasingly demonstrated to be an extremely beneficial therapy in different forms of cardiovascular disease. This review provides a summary of the knowledge that exists on aldosterone actions in the cardiovascular system and, in providing the translational impact of this knowledge to the clinical arena, illustrates how much more needs to be achieved in exploring the use of mineralocorticoid receptor blockers in less advanced stages of heart, renal, and vascular disease.
Rationale for targeting the immune system through checkpoint molecule blockade in the treatment of non-small-cell lung cancer
Authors: C. Zielinski, S. Knapp, C. Mascaux, F. Hirsch
Journal: Annals of Oncology (2013)

Treatments of non-small-cell lung cancer (NSCLC)-particularly of the squamous subtype-are limited. In this article, we describe the immunomodulatory environment in NSCLC and the potential for therapeutic targeting of the immune system through cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) immune-checkpoint pathway blockade.
Intolerance to Statins: Mechanisms and Management
Authors: Rafael Bitzur, Hofit Cohen, Yehuda Kamari, Dror Harats
Journal: Diabetes Care (2013)

Statins are considered very effective in reducing cardiovascular morbidity and mortality in high-risk patients. However, although adherence to statins improves morbidity and mortality (1), it remains suboptimal (2). One of the most important causes of nonadherence is the so-called statin intolerance, mainly because of muscle-related symptoms. These symptoms most often consist of myalgia unaccompanied by significant creatine kinase (CK) elevations. Less often, myositis (elevated CK >10 times the upper limit of normal) or rhabdomyolysis (CK level >10,000 IU/L or accompanied by significant elevation in creatinine level) develops.

In randomized controlled trials, the incidence of statin myopathy is ~1.5–5.0% (3). However, this low incidence may be misleading for several reasons. First, in most studies patients with a history of statin intolerance were excluded. Other studies had a single-blinded statin run-in phase, and patients experiencing muscle-related symptoms or CK elevations during this phase were excluded. Patients who tend to be at risk for developing muscle-related symptoms, such as women, elderly patients, and patients with significant comorbidity, who comprise a large proportion of statin-treated patients in real-life settings, are underrepresented in randomized controlled trials. Some studies have defined muscle-related effects by elevated CK levels only, disregarding myalgia. Last but not least, patients enrolled in studies might be motivated and so minimize reporting of mild myalgias, thus leading to underestimation of the magnitude of the problem.

Data concerning real-life incidence of statin-related myopathy are scarce. In the Prediction of Muscular Risk in Observational Conditions (PRIMO) study (4), 7,924 patients receiving high-dosage statin therapy in an outpatient setting in France were asked about muscle-related symptoms. Overall, muscular symptoms were reported by 10.5% of the patients. A weakness of this study is that it lacked a comparison/control group not treated with statins. In a study of adults aged ≥40 years who participated in National Health and …
Is EGFR expression important in non-small cell lung cancer?
Authors: S M Lee
Journal: Thorax (2006)

There are still many unanswered questions on the use of EGFR treatment in NSCLC

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is frequently overexpressed in non-small cell lung cancer (NSCLC). These receptors play an important role in tumour cell survival and activated phosphorylated EGFR results in the phosphorylation of downstream proteins that cause cell proliferation, invasion, metastasis, and inhibition of apoptosis. Expression appears to be dependent on histological subtypes, most frequently expressed in squamous cell carcinoma but also frequently expressed in adenocarcinomas and large cell carcinomas.1 Not surprisingly, there are many published reports attempting to correlate the relationship between EGFR protein overexpression and survival. However, the data regarding the prognostic role of EGFR expression are inconsistent and confusing, with some reports indicating that EGFR is associated with poor survival while no prognostic association was seen in other reports.

In this issue of Thorax Nakamura et al carried out a meta-analysis of 18 studies (including nearly 3000 patients), reviewing whether EGFR overexpression has an impact on survival. Most of these reported studies evaluated EGFR protein expression by immunohistochemistry (IHC) and it is possible that different conclusions may reflect differences in incubation and detection methods, reagents, assay cut off points, and population studied with different stages. Nevertheless, EGFR overexpression was seen in 39% in adenocarcinoma, 58% in squamous cell carcinoma, and 38% in large cell carcinoma, and they concluded that EGFR protein overexpression using …
Inflammatory endobronchial polyposis with bronchiectasis in cystic fibrosis
Authors: C. Roberts, A.M. Devenny, R. Brooker, J.S. Cockburn, K.M. Kerr
Journal: European Respiratory Journal (2001)

An unusual case of endobronchial polyposis associated with extensive bronchiectasis in the context of cystic fibrosis (CF) has been described. A 15-yr-old female patient with CF underwent partial pneumonectomy for extensive bronchiectasis and frequent infective pulmonary exacerbations. Cylindrical bronchiectasis with associated purulent bronchitis and bronchiolitis, together with inflammatory polyposis, was noted in the resected lung. To the best of the authors' knowledge, this is the first report of multiple endobronchial polyposis and may represent a rare complication of bronchiectasis in a patient with cystic fibrosis. On-going infection and the cellular composition of the polyps are discussed in relation to their possible aetiological relevance and relationship to upper respiratory tract polyps.
Giant lymph node hyperplasia of the lung (Castleman's disease) associated with recurrent pleural effusion.
Authors: A A Awotedu, B A Otulana, C O Ukoli
Journal: Thorax (1990)

A case of giant lymph node hyperplasia (Castleman9s disease) of the lung presented with pleural effusion (which was recurrent), an unusual complication. The patient was treated with pneumonectomy and has survived for three years without relapse. This is the first report of the disease from black Africa.
Clonal, cultured, murine fetal liver hepatoblasts maintain liver specification in chimeric mice
Authors: Charles E. Rogler, Hong Chou Zhou, Lauretta LeVoci, Leslie E. Rogler
Journal: Hepatology (2007)

Recent studies have shown a pluripotential nature of stem cells that were previously thought to be committed to specific lineages. HBC-3 cells are a clonal fetal murine hepatoblast cell line derived from an e9.5 murine embryo, and these cells can be induced to form hepatocytes and bile ducts in vitro and when transplanted into adult mouse livers. To determine whether HBC-3 cells can exhibit a pluripotential phenotype, we created chimeric mice by injection of enhanced green fluorescent protein (EGFP)-marked HBC-3 cells into wild-type or dipeptidyl dipeptidase IV (DPPIV) knockout blastocysts. Genetically labeled HBC-3 cells were identified by EGFP polymerase chain reaction (PCR) in all the major organs of many chimeric mice and visualized in chimeras as bright red DPPIV-positive cells in the DPPIV knockout chimeric mice. Strikingly, the HBC-3 cells maintained phenotypic and biochemical features of liver specification in every case in which they were identified in nonliver organs, such as brain, mesenchyme, and bone. In adult liver they were present as small foci of hepatocytes and bile ducts in the chimeras. Additional major histocompatibility complex (MHC) marker analysis and X and Y chromosome content analysis further demonstrated that HBC-3 cells did not acquire the phenotype of the organs in which they resided and that they were not present because of fusion with host cells.In contrast to other stem cell types, these data demonstrate that cultured murine fetal liver stem cells appear to maintain their liver specification in the context of nonliver organs in chimeric mice.
MicroRNA-486–dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy–associated symptoms
Authors: Matthew S. Alexander, Juan Carlos Casar, Norio Motohashi, Natássia M. Vieira, Iris Eisenberg, Jamie L. Marshall, Molly J. Gasperini, Angela Lek, Jennifer A. Myers, Elicia A. Estrella, Peter B. Kang, Frederic Shapiro, Fedik Rahimov, Genri Kawahara, Jeffrey J. Widrick, Louis M. Kunkel
Journal: Journal of Clinical Investigation (2014)

Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, which results in dysfunctional signaling pathways within muscle. Previously, we identified microRNA-486 (miR-486) as a muscle-enriched microRNA that is markedly reduced in the muscles of dystrophin-deficient mice (Dmdmdx-5Cv mice) and in DMD patient muscles. Here, we determined that muscle-specific transgenic overexpression of miR-486 in muscle of Dmdmdx-5Cv mice results in reduced serum creatine kinase levels, improved sarcolemmal integrity, fewer centralized myonuclei, increased myofiber size, and improved muscle physiology and performance. Additionally, we identified dedicator of cytokinesis 3 (DOCK3) as a miR-486 target in skeletal muscle and determined that DOCK3 expression is induced in dystrophic muscles. DOCK3 overexpression in human myotubes modulated PTEN/AKT signaling, which regulates muscle hypertrophy and growth, and induced apoptosis. Furthermore, several components of the PTEN/AKT pathway were markedly modulated by miR-486 in dystrophin-deficient muscle. Skeletal muscle–specific miR-486 overexpression in Dmdmdx-5Cv animals decreased levels of DOCK3, reduced PTEN expression, and subsequently increased levels of phosphorylated AKT, which resulted in an overall beneficial effect. Together, these studies demonstrate that stable overexpression of miR-486 ameliorates the disease progression of dystrophin-deficient skeletal muscle.
H-2Kd-restricted antigenic peptides share a simple binding motif.
Authors: P Romero, G Corradin, I F Luescher, J L Maryanski
Journal: The Journal of Experimental Medicine (1991)

We have defined structural features that are apparently important for the binding of four different, unrelated antigenic epitopes to the same major histocompatibility complex (MHC) class I molecule, H-2Kd. The four epitopes are recognized in the form of synthetic peptides by cytotoxic T lymphocytes of the appropriate specificity. By analysis of the relative potency of truncated peptides, we demonstrated that for each of the four epitopes, optimal antigenic activity was present in a peptide of 9 or 10 amino acid residues. A comparison of the relative competitor activity of the different-length peptides in a functional competition assay, as well as in a direct binding assay based on photoaffinity labeling of the Kd molecule, indicated that the enhanced potency of the peptides upon reduction in length was most likely due to a higher affinity of the shorter peptides for the Kd molecule. A remarkably simple motif that appears to be important for the specific binding of Kd-restricted peptides was identified by the analysis of peptides containing amino acid substitutions or deletions. The motif consists of two elements, a Tyr in the second position relative to the NH2 terminus and a hydrophobic residue with a large aliphatic side chain (Leu, Ile, or Val) at the COOH-terminal end of the optimal 9- or 10-mer peptides. We demonstrated that a simple peptide analogue (AYP6L) that incorporates the motif can effectively and specifically interact with the Kd molecule. Moreover, all of the additional Kd-restricted epitopes defined thus far in the literature contain the motif, and it may thus be useful for the prediction of new epitopes recognized by T cells in the context of this MHC class I molecule.
Circulating Galectin-3 Promotes Metastasis by Modifying MUC1 Localization on Cancer Cell Surface
Authors: Qicheng Zhao, Xiuli Guo, Gerard B. Nash, Philip C. Stone, John Hilkens, Jonathan M. Rhodes, Lu-Gang Yu
Journal: Cancer Research (2009)

Abstract Adhesion of circulating tumor cells to the blood vessel endothelium is a critical step in cancer metastasis. We show in this study that galectin-3, the concentration of which is greatly increased in the circulation of cancer patients, increases cancer cell adhesion to macrovascular and microvascular endothelial cells under static and flow conditions, increases transendothelial invasion, and decreases the latency of experimental metastasis in athymic mice. These effects of galectin-3 are shown to be a consequence of its interaction with cancer-associated MUC1, which breaks the “protective shield” of the cell-surface MUC1 by causing MUC1 polarization, leading to exposure of smaller cell-surface adhesion molecules/ligands including CD44 and ligand(s) for E-selectin. Thus, the interaction in the bloodstream of cancer patients between circulating galectin-3 and cancer cells expressing MUC1 bearing the galectin-3 ligand TF (Galβ1,3GalNAc-) promotes metastasis. This provides insight into the molecular regulation of metastasis and has important implications for the development of novel therapeutic strategies for prevention of metastasis. [Cancer Res 2009;69(17):6799–806]
Prototype Nerve-Specific Near-Infrared Fluorophores
Authors: Min Ho Park, Hoon Hyun, Yoshitomo Ashitate, Hideyuki Wada, GwangLi Park, Jeong Heon Lee, Costyl Njiojob, Maged Henary, John V. Frangioni, Hak Soo Choi
Journal: Theranostics (2014)

Nerve preservation is an important issue during most surgery because accidental transection or injury results in significant morbidity, including numbness, pain, weakness, or paralysis.Currently, nerves are still identified only by gross appearance and anatomical location during surgery, without intraoperative image guidance.Near-infrared (NIR) fluorescent light, in the wavelength range of 650-900 nm, has the potential to provide high-resolution, high-sensitivity, and real-time avoidance of nerve damage, but only if nerve-specific NIR fluorophores can be developed.In this study, we evaluated a series of Oxazine derivatives to highlight various peripheral nerve structures in small and large animals.Among the targeted fluorophores, Oxazine 4 has peak emission near into the NIR, which provided nerve-targeted signal in the brachial plexus and sciatic nerve for up to 12 h after a single intravenous injection.In addition, recurrent laryngeal nerves were successfully identified and highlighted in real time in swine, which could be preserved during the course of thyroid resection.Although optical properties of these agents are not yet optimal, chemical structure analysis provides a basis for improving these prototype nerve-specific NIR fluorophores even further.
ERS/ATS statement on interventional pulmonology
Authors: J.F. Beamis, H.D. Becker, S. Cavaliere, H. Colt, J.P. Diaz-Jimenez, J.F. Dumon, E. Edell, K.L. Kovitz, H.N. Macha, A.C. Mehta, M. Marel, M. Noppen, J. Strausz, T.G. Sutedja
Journal: European Respiratory Journal (2002)

We investigated whether the time between synthesis and injection and the resulting decrease in specific activity affects the normal-organ and tumor uptake of the PSMA ligand <sup>18</sup>F-rhPSMA-7.3 in patients with prostate cancer. <b>Methods:</b> The biodistribution of <sup>18</sup>F-rhPSMA-7.3 on PET/CT scans obtained with a high specific activity (median, 178.9 MBq/µg; <i>n</i> = 42) and a low specific activity (median, 19.3 MBq/µg; <i>n</i> = 42) was compared. <b>Results:</b> Tracer uptake by the parotid gland, submandibular gland, and spleen was moderately but significantly lower in the low-specific-activity group than in the high-specific-activity group (median SUV<sub>mean</sub>, 16.7 vs. 19.2; 18.1 vs. 22.3; and 7.8 vs. 9.6, respectively). No other statistically significant differences were found for normal organs or tumor lesions. <b>Conclusion:</b> A 10-fold decrease in specific activity has only minor effects on the biodistribution of <sup>18</sup>F-rhPSMA-7.3. These findings suggest that <sup>18</sup>F-labeled PSMA ligands can be centrally produced and shipped to PET clinics in a similar way to <sup>18</sup>F-FDG.
Pulmonary alveolar microlithiasis
Authors: F. Giallauria, G. Giallauria
Journal: Thorax (2011)

Pulmonary alveolar microlithiasisA 37-year-old patient was admitted to the hospital with severe dyspnoea and cough.Baseline investigations revealed haemoglobin of 16.2 g/dl, haematocrit of 48.8% and a total leucocyte count of 8800/mm 3 .Comprehensive metabolic profile and serum and urine protein electrophoresis findings were normal.Arterial blood gas analysis showed type 1 respiratory failure.Spirometry showed restrictive ventilatory disturbances (vital capacity 53%, forced expiratory volume in 1 s 91%).A posterioreanterior chest radiograph showed bilateral diffuse, nodular ('sandstorm-like') calcifications in both lungs (figure 1A).A high-resolution CTscan demonstrated multiple bilateral micronodulation of calcific densities throughout both lungs (figure 1B).On transbronchial biopsy, the diagnosis of massive parenchymal and alveolar calcification was confirmed.Echocardiography showed valve calcification with moderate mitral-aortic regurgitation and severe pulmonary hypertension.Abdominal ultrasonography revealed cholelithiasis and medullary nephrocalcinosis.The diagnosis of pulmonary alveolar microlithiasis (PAM) with concomitant valve calcification, cholelithiasis and idiopathic medullary nephrocalcinosis was established.
Attenuation of Tumor Growth by Formation of Antiproliferative Glycosaminoglycans Correlates with Low Acetylation of Histone H3
Authors: Ulrika Nilsson, Richard Johnsson, Lars-Åke Fransson, Ulf Ellervik, Katrin Mani
Journal: Cancer Research (2010)

Abstract Glycosaminoglycan (GAG) chains anchored to core proteins form proteoglycans, widely distributed cell-surface macromolecules with multiple functions, such as regulation of growth factor and cytokine signaling, cell-cell interactions, and uptake of biomolecules. The biosynthesis of GAG can be manipulated by xylosides attached to various hydrophobic groups, and we have earlier reported that a naphthoxyloside, 2-(6-hydroxynaphthyl) β-d-xylopyranoside (XylNapOH), which serves as a primer for GAG synthesis, reduces tumor load up to 97% in vivo, despite lower efficiency in vitro. Here we show, using radiolabeled xylosides and coculture experiments, that XylNapOH-treated bladder and breast carcinoma cells secrete antiproliferative GAG chains that are taken up by both normal and cancer cells and transported to the cell nuclei where they induce an antiproliferative effect, accompanied by apoptosis. We also show that XylNapOH treatment lowers the level of histone H3 acetylation selectively in bladder and breast carcinoma cells without affecting expression of histone H3. However, XylNapOH-primed GAG chains from normal cells are not internalized and do not cause growth retardation. Using in vitro and in vivo C6 glioma cell and tumor models, we show that XylNapOH is much more effective in vivo than in vitro. We propose that, in vivo, the antiproliferative XylNapOH-primed GAG chains produced by tumor cells inhibit tumor growth in an autocrine fashion by formation of antiproliferative GAG chains on the xyloside prodrug, whereas no antiproliferative GAG chains are produced by surrounding normal cells. This is a novel mechanism for targeting tumor cells, making these xylosides promising drug candidates for antitumor therapy. Cancer Res; 70(9); 3771–9. ©2010 AACR.