tbuckley/cabot-search huggingface dataset:
Collagen phagocytosis by lung alveolar macrophages in animal models of emphysema
Authors: M. Lucattelli, E. Cavarra, M. M. de Santi, T.D. Tetley, P.A. Martorana, G. Lungarella
Journal: European Respiratory Journal (2003)

Under steady state conditions the intracellular pathway is the major route of collagen catabolism in tissues characterised by rapid collagen turnover. In the lung, the collagen is subject to continuous remodelling and turnover however, the intracellular pathway of collagen degradation is unusual under physiological conditions. The current authors previously described crystalloid inclusions in alveolar macrophages of mice with genetic emphysema at the time of septal disruption. Using an immunogold technique these inclusions were identified as collagen-derived products and related to intracytoplasmic collagen degradation. To examine whether a different degree of protease burden in lung interstitium may influence the route of intracellular collagen degradation, collagen phagocytosis by alveolar macrophages was studied in various mouse models of emphysema at the time when emphysema develops. Evident collagen by-products in alveolar macrophages were observed in destructive processes characterising spontaneous models of emphysema either with negligible (blotchy mouse) or moderate (pallid mouse) elastase burden. On the other hand, intracellular collagen by-products were appreciated only in a few macrophages from tight-skin mice with high elastolytic burden and could not be observed in mice with a very severe burden after elastase instillation. In conclusion, the interstitial level of proteases burden can affect the way by which the collagen is cleared (intracellularly versus extracellularly).
Nonrandom Wolbachia Infection Status of Drosophila melanogaster Strains with Different mtDNA Haplotypes
Authors: Maria D. S. Nunes, Viola Nolte, Christian Schlötterer
Journal: Molecular Biology and Evolution (2008)

Wolbachia are maternally inherited bacteria, which typically spread in the host population by inducing cytoplasmic incompatibility (CI). In Drosophila melanogaster, Wolbachia is quite common but CI is variable, with most of the studies reporting low levels of CI. Surveying mitochondrial DNA (mtDNA) variation and infection status in a worldwide D. melanogaster collection, we found that the Wolbachia infection was not randomly distributed among flies with different mtDNA haplotypes. This preferential infection of some mtDNA haplotypes could be caused by a recent spread of mtDNA haplotypes associated with the infection. The comparison of contemporary D. melanogaster samples with lines collected more than 50 years ago shows that indeed one haplotype with a high incidence of Wolbachia infection has increased in frequency. Consistent with this observation, we found that the acquisition of a Wolbachia infection in a population from Crete was accompanied with an almost complete mtDNA replacement, with the Wolbachia-associated haplotype becoming abundant. Although it is difficult to identify the evolutionary forces causing the global increase of wMel, the parallel sweep of Wolbachia and an mtDNA haplotype suggests a fitness advantage of the Wolbachia infection.
The Simpleton’s Error in Drug Development
Authors: Michael Castro
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.99.183 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12454124 The Simpleton’s Error in Drug Development Michael CastroxMichael CastroSearch for articles by this author Show More The Charles Wood Cancer Center, Glens Falls, NY https://doi.org/10.1200/JCO.2002.99.183 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Mechanical stimuli exciting type A atrial vagal receptors in the cat.
Authors: G Recordati, F Lombardi, V S Bishop, A Malliani
Journal: Circulation Research (1976)

The activity of type A right atrial vagal receptors was recorded from the right cervical vagus in cats anesthetized with sodium pentobarbital, immobilized with gallamine, and with their chests open. Nerve impulses initiated by receptor activation were recorded simultaneously with instantaneous right atrial pressure and dimensional changes under various hemodynamic conditions. Atrial volume changes induced by infusion of saline, bleeding, and occlusion of the inferior vena cava did not alter consistently the systolic activity of the receptors. Electrical stimulation of the right stellate ganglion significantly increased the frequency of discharge during systole, whereas electrical stimulation of the left thoracic vagus significantly reduced the frequency of discharge. These inotropic interventions produced similar effects when the heart was paced at a fixed rate. Pacing the right atrial appendage increased the systolic discharge of the receptors only when at high rates the atrium contracted against closed atrioventricular valves. To investigate the influence of tonic efferent sympathetic activity on spontaneous receptor discharge, three receptors were studied before and after bilateral surgical stellectomy, and in cats with their chest closed three receptors were studied before and after infusion of propranolol. Both of these interventions markedly reduced the systolic activity. In addition to having effects on systolic activity, injection of saline, vagal stimulation, and sympathetic "denervation" always activated the receptors during filling. Our results indicate that: (1) the systolic discharge of type A receptors is a function of the active tension developed by atrial muscle during contraction; and (2) the pattern of discharge of the receptors during the atrial cycle depends on both the degree of atrial distention and the state and extent of contraction.
Friends of the Oppressed Foot?
Authors: Andrew J. M. Boulton, Edward B. Jude
Journal: Diabetes Care (2001)

The title of this editorial originates from an article in the “Herald Tribune” from 1889 entitled “Think of the Feet,” which stated that the human foot is cruelly oppressed in the civilized world. It remarked that shoes were made too tight and “in utter defiance of the shape of the foot,” resulting in “the foot being outraged from morning till night.” Readers of Diabetes Care in the new millennium may well ask, “what has changed in the last 110 years?” When Ella Fitzgerald was interviewed in 1993 and asked what resulted in her major amputations, she replied, “I liked to wear pointy-toed evening shoes.” Today, despite major steps in our understanding of the pathogenesis of diabetic foot disease, there is no evidence of any consistent reduction in amputation rates among diabetic patients in …
Green Tea Component, Catechin, Induces Apoptosis of Human Malignant B Cells via Production of Reactive Oxygen Species
Authors: Tomonori Nakazato, Keisuke Ito, Yasuo Ikeda, Masahiro Kizaki
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Green tea polyphenol, (−)-epigallocatechin-3-gallate, has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The aim of this study was to investigate the possibility of (−)-epigallocatechin-3-gallate as a novel therapeutic agent for the patients with B-cell malignancies including multiple myeloma. Experimental Design: We investigated the effects of (−)-epigallocatechin-3-gallate on the induction of apoptosis in HS-sultan as well as myeloma cells in vitro and further examined the molecular mechanisms of (−)-epigallocatechin-3-gallate-induced apoptosis. Results: (−)-Epigallocatechin-3-gallate rapidly induced apoptotic cell death in various malignant B-cell lines in a dose- and time-dependent manner. (−)-Epigallocatechin-3-gallate-induced apoptosis was in association with the loss of mitochondrial transmembrane potentials (Δψm); the release of cytochrome c, Smac/DIABLO, and AIF from mitochondria into the cytosol; and the activation of caspase-3 and caspase-9. Elevation of intracellular reactive oxygen species (ROS) production was also shown during (−)-epigallocatechin-3-gallate-induced apoptosis of HS-sultan and RPMI8226 cells as well as fresh myeloma cells. Antioxidant, catalase, and Mn superoxide dismutase significantly reduced ROS production and (−)-epigallocatechin-3-gallate-induced apoptosis, suggesting that ROS plays a key role in (−)-epigallocatechin-3-gallate-induced apoptosis in B cells. Furthermore, a combination with arsenic trioxide (As2O3) and (−)-epigallocatechin-3-gallate significantly enhanced induction of apoptosis compared with As2O3 alone via decreased intracellular reduced glutathione levels and increased production of ROS. Conclusions: (−)-Epigallocatechin-3-gallate has potential as a novel therapeutic agent for patients with B-cell malignancies including multiple myeloma via induction of apoptosis mediated by modification of the redox system. In addition, (−)-epigallocatechin-3-gallate enhanced As2O3-induced apoptosis in human multiple myeloma cells.
Rapid spread of the novel respiratory syncytial virus A ON1 genotype, during the epidemic seasons 2011-2013
Authors: Ambra Nicolai, Stefano Papasso, Marianna Ferrara, Carolina Scagnolari, Isabella Calicchia, Concetta Schiavariello, Marianna Eleonora Grande, Claudia Alessandroni, Marco Mariani, Alessandra Pierangeli, Fabio Midulla
Journal: European Respiratory Journal (2014)

Background  Respiratory Syncytial Virus (RSV) is a major cause of lower respiratory-tract infection in infants. Based on reactions with monoclonal antibodies against glycoproteins G, RSV has been classified into subtypes A and B.  Aim  In this study, RSV-A positive cases were genotyped to evaluate the genetic variability which can modify RSV epidemic and clinical severity.  Methods  During 3 epidemic seasons children presenting with respiratory symptoms at the Pediatric Emergency, “Sapienza” University of Rome (RM), and at the Pediatric Department of Marche Polytechnic University (AN)were enrolled and tested for RSV with PCR on nasal washings. RSV positive samples were randomly selected for genomic characterization. Demographic and clinical data were taken from patients9 medical files. Results  515 RSV-positive infants were detected: 165 in RM (median age 2.75m; range 0.2-29m) and 350 in AN (median age 3.0m; range 0.1-163m). 161/360 RSV-A positive samples were sequenced. 15 in RM and 51 in AN strains grouped with the novel genotype ON1 which is characterized by a 72-nt insertion in G resulting in 24 extra aa. ON1 was not detected in RM neither in AN samples during 2010-11 season; it accounted for 14/61 strains (22.9%) analyzed in 2011-12 and for 52/59 strains (88.1%) in 2012-13. Clinical data showed that ON1 infection was more frequent in younger infants and caused less frequently a severe disease. Conclusion  We document the presence of ON1 genotype in Italy in the 2011-12 epidemic season and its rapid spread in 2012-13. The novel genotype does not seem to possess special severity determinants compared with previously circulating RSV-A strains.
Mutant Caveolin-3 Induces Persistent Late Sodium Current and Is Associated With Long-QT Syndrome
Authors: Matteo Vatta, Michael J. Ackerman, Bin Ye, Jonathan C. Makielski, Enoh E. Ughanze, Erica W. Taylor, David J. Tester, Ravi C. Balijepalli, Jason D. Foell, Zhaohui Li, Timothy J. Kamp, Jeffrey A. Towbin
Journal: Circulation (2006)

Background— Congenital long-QT syndrome (LQTS) is a primary arrhythmogenic syndrome stemming from perturbed cardiac repolarization. LQTS, which affects ≈1 in 3000 persons, is 1 of the most common causes of autopsy-negative sudden death in the young. Since the sentinel discovery of cardiac channel gene mutations in LQTS in 1995, hundreds of mutations in 8 LQTS susceptibility genes have been identified. All 8 LQTS genotypes represent primary cardiac channel defects (ie, ion channelopathy) except LQT4, which is a functional channelopathy because of mutations in ankyrin-B. Approximately 25% of LQTS remains unexplained pathogenetically. We have pursued a “final common pathway” hypothesis to elicit novel LQTS-susceptibility genes. With the recent observation that the LQT3-associated, SCN5A -encoded cardiac sodium channel localizes in caveolae, which are known membrane microdomains whose major component in the striated muscle is caveolin-3, we hypothesized that mutations in caveolin-3 may represent a novel pathogenetic mechanism for LQTS. Methods and Results— Using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing, we performed open reading frame/splice site mutational analysis on CAV3 in 905 unrelated patients referred for LQTS genetic testing. CAV3 mutations were engineered by site-directed mutagenesis and the molecular phenotype determined by transient heterologous expression into cell lines that stably express the cardiac sodium channel hNa v 1.5. We identified 4 novel mutations in CAV3 -encoded caveolin-3 that were absent in &gt;1000 control alleles. Electrophysiological analysis of sodium current in HEK293 cells stably expressing hNa v 1.5 and transiently transfected with wild-type and mutant caveolin-3 demonstrated that mutant caveolin-3 results in a 2- to 3-fold increase in late sodium current compared with wild-type caveolin-3. Our observations are similar to the increased late sodium current associated with LQT3-associated SCN5A mutations. Conclusions— The present study reports the first CAV3 mutations in subjects with LQTS, and we provide functional data demonstrating a gain-of-function increase in late sodium current.
Prevalence of stenotic changes in arteries supplying the lumbar spine. A postmortem angiographic study on 140 subjects
Authors: L. I Kauppila
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> To study the prevalence of arterial diseases in the arteries supplying the lumbar spine and their relation to other vascular diseases, as well as to chronic low back pain. <h3>METHODS</h3> Five pairs of the lumbar arteries and the middle sacral artery were evaluated from 140 postmortem aortograms, performed in connection with routine medicolegal necropsies on subjects ranging from 16 to 89 years of age. For information about low back pain history, a close relative of each of the deceased was interviewed two to four weeks after the necropsy. <h3>RESULTS</h3> Twenty one (22%) men and nine (20%) women had occluded arteries, and an additional 33 (35%) men and 17 (38%) women had narrowed arteries. The mean age for men with occluded or narrowed arteries, or both, was 50 years and for women 59 years. Most of the stenotic changes were seen at the orifices or in the first part of the arteries. The middle sacral artery was most often affected, followed by the fourth lumbar arteries. The number of collateral arteries increased with occluded (p &lt;0.001) and narrowed arteries (p = 0.001). Stenotic lumbar/middle sacral arteries were found, on average, five years earlier than atherosclerosis of the coronary arteries. Subjects with one or more occluded/narrowed arteries were 8.5 times more likely to have suffered from chronic (that is, three months or longer) low back pain at some time during their life than were those without such findings (odds ratio adjusted for age and sex 8.5; 95% confidence intervals 2.9, 24; p &lt;0.001). <h3>CONCLUSIONS</h3> The study shows that the lumbar and middle sacral arteries frequently become obliterated by atheromatous lesions during adult life, and that obliteration of these arteries is more common in subjects with a history of chronic back pain than in those without.
Heterophile Antibodies Masquerade as Interferon-α in Subjects With New-Onset Type 1 Diabetes
Authors: Theresa Aly, Devasenan Devendra, Jennifer Barker, Edwin Liu, Liping Yu, George S. Eisenbarth
Journal: Diabetes Care (2004)

One of the potential environmental triggers in type 1 diabetes may be viruses. The mechanism of viral infections leading to β-cell destruction of the pancreas is becoming clearer, and the potential role of viruses inducing the cytokine interferon-α (IFN-α) has been implicated. It is well established that IFN-α therapy induces islet cell autoimmunity and other endocrine autoantibodies as well (1). Recent studies have indicated that IFN-α levels in serum of new-onset type 1 diabetic subjects are elevated and perhaps related to recent enteroviral infections (2,3). These studies suggest that IFN-α may be a useful surrogate marker for disease onset, perhaps due to a recent viral infection or vaccination.

At the Barbara Davis Center for Childhood Diabetes in Denver, Colorado, we screened 32 new-onset type 1 diabetic subjects and 31 …
A General Tendency for Conservation of Protein Length Across Eukaryotic Kingdoms
Authors: D. Wang
Journal: Molecular Biology and Evolution (2004)

Protein elongation can occur in many ways, such as domain duplication or insertion and as recruitment of a transposable element fragment into the coding region, and it is believed to be a general tendency in protein evolution. Indeed, a previous study showed that yeast proteins are, on average, longer than their orthologs in bacteria, and in this study, we found that proteins in yeast, nematode, Drosophila, human, and Arabidopsis are, on average, longer than their orthologs in Escherichia coli. Surprisingly, however, we found conservation of protein sequence length across eukaryotic kingdoms. We collected 1,252 orthologous proteins from yeast, nematode, Drosophila, human, and Arabidopsis and found that the total length of these proteins is very similar among the five species and that there is no general tendency for a protein to increase or decrease in length. Furthermore, although paralogous proteins tend to undergo more sequence-length changes, there is also no general tendency for length increase. However, proteins that are commonly shared by Drosophila and human but not by yeast are, on average, substantially longer than proteins that are shared by yeast, Drosophila, and human. This is a puzzle that begs for an answer.
Biweekly pegylated liposomal doxorubicin in patients with relapsed ovarian cancer: results of a multicenter phase-II trial
Authors: J. Sehouli, G. Oskay-Özcelik, J. Kühne, D. Stengel, H.-J. Hindenburg, P. Klare, G. Heinrich, B. Schmalfeldt, H. Mertens, O. Camara, W. Lichtenegger
Journal: Annals of Oncology (2006)
Uniform high frequency expression of autoantibody-associated crossreactive idiotypes in the primary B cell follicles of human fetal spleen.
Authors: T J Kipps, B A Robbins, D A Carson
Journal: The Journal of Experimental Medicine (1990)

At 23 wk of gestation, the fetal spleen contains follicles of lymphocytes that coexpress B cell differentiation antigens, surface Ig, and the 67-kD pan-T lymphocyte antigen, CD5 (Leu-1). Such cells are thought to represent the normal equivalent cells of B chronic lymphocytic leukemia (CLL). This B cell leukemia is distinctive in that high proportions of patients have leukemic cells that express sIg bearing one or more crossreactive idiotypes (CRIs) that commonly are found on IgM autoantibodies. We performed immunohistochemical studies on fetal spleen at 23 wk of gestation using a panel of mAbs specific for autoantibody-associated CRIs. We find that high proportions (5-17%) of the lymphocytes within each follicle react with any one of the anti-CRI mAbs. Furthermore, there is little variation between primary follicles in the proportions of cells that express a particular CRI. Using a cocktail of four anti-CRI mAbs, we detect autoantibody-associated CRIs on approximately one-third of the lymphocytes within each of the primary B cell follicles. These data indicate that the many of the Igs produced during early B cell development may be structurally related to IgM autoantibodies and to Ig expressed in CLL and related CD5 B cell malignancies. Furthermore, these studies suggest that the repertoire of Ig V genes expressed in each primary B cell follicle may be representative of the total restricted Ig V gene repertoire expressed during early B cell ontogeny.
Uterine Fibroids after the Menopause
Authors: W. F. Shaw
Journal: BMJ (1927)

EDICA JOURKS 919 remembered that it is wellnigh impossible for ainy one investigator to conduct experimentation oni a sufficiently large scale, and that it is therefore desirable that experi- ments of this kind should be multiplied so that out of a considerable series adequate data may be secured.So far as they go, the present figures tend to support the conten- tion .that the time of service in relation to the oestrous cycle is a factor of no importance in the matter of thle determination of sex in the mammal.SiImmar,y.In an experiment designed to examine the sex ratio among individuals resultiing from coitus dfiiring the fiist three lhours and during the last tliree hours of oestrus respectively in the rat, no difference was noted between these two groups.
SM22α Modulates Vascular Smooth Muscle Cell Phenotype During Atherogenesis
Authors: Susanne Feil, Franz Hofmann, Robert Feil
Journal: Circulation Research (2004)

The function of cytoskeletal proteins in the modulation of vascular smooth muscle cell (SMC) phenotype during vascular disease is poorly understood. In this report, we used a combination of gene targeting and Cre/lox-mediated cell fate mapping in mice to investigate the role of SM22α, an SMC-specific cytoskeletal protein of unknown function, in the development of atherosclerosis. In hypercholesterolemic ApoE-deficient mice, genetic ablation of SM22α resulted in increased atherosclerotic lesion area and a higher proportion of proliferating SMC-derived plaque cells. These results identify a role for SM22α in the regulation of SMC phenotype during atherogenesis.
Ulcerative colitis during CTLA-4Ig therapy in a patient with rheumatoid arthritis
Authors: L M Amezcua-Guerra, B Hernández-Martínez, C Pineda, R Bojalil
Journal: Gut (2006)

The coexistence of rheumatoid arthritis (RA) and ulcerative colitis (UC) is exceptional, with only a few cases reported in the literature.1–4 However, the current use of biological agents can modify the balance of inflammatory mediators and the lymphocytic profiles of the original disease, promoting the emergence of additional conditions. This seems to be the case for a patient with severe RA who developed UC while being treated with CTLA-4Ig (abatacept).

We report the case of a 55 year old male with a seven year history of seropositive RA refractory to treatment with 20 mg/week methotrexate (MTX), 1.5 g/day sulphasalazine (SSZ), 400 mg/day hydroxychloroquine, and 100 mg/day azathioprine. The patient was included in an CTLA-4Ig (10 mg/kg intravenously monthly) …