tbuckley/cabot-search huggingface dataset:
Adaptation of canine saphenous veins to grafting. Correlation of contractility and contractile protein content.
Authors: C L Seidel, R M Lewis, R Bowers, R D Bukoski, H S Kim, J C Allen, C Hartley
Journal: Circulation Research (1984)

Saphenous veins are used extensively to replace stenotic coronary arteries. However, the contractile and biochemical adaptations of grafted veins are unknown. The three purposes of this work were to characterize the contractile properties of grafted veins, to determine whether altered contractile characteristics were associated with quantitative changes in actin, myosin and collagen, and to determine which changes were associated with the surgical procedure and which with placement in the arterial circulation. Canine saphenous veins were removed and returned to their original location (venous autograft), while others were used to replace a segment of femoral artery (arterial graft). The grafts were removed 1, 4, and 8 weeks later and compared with the contralateral saphenous vein. Both graft types exhibited an increase in sensitivity to norepinephrine but not to potassium chloride. The venous autograft exhibited a reversible reduction in myosin content and in maximum contractile response (force/cross-sectional area) to potassium chloride and norepinephrine. In contrast, the arterial graft exhibited increased wall thickness and content of all measured proteins and decreased maximum contractile response. The latter occurred even though there was an increase in the net production of actin and myosin. Expressing the maximum contractile response in terms of the myosin content did not normalize the contractile response. These results suggest that, except for the elevated sensitivity to norepinephrine, the vein is capable of recovering from the effects of surgery within 8 weeks; however, placement of the vein in the arterial circulation delays this recovery and initiates a hypertrophic response that includes an attenuation of contractile function.
Low serum levels of vitamin D in idiopathic inflammatory myopathies
Authors: Payam Azali, Sevim Barbasso Helmers, Ingrid Kockum, Tomas Olsson, Lars Alfredsson, Peter J Charles, Karin Piehl Aulin, Ingrid E Lundberg
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To evaluate serum levels of 25(OH) vitamin D in patients with idiopathic inflammatory myopathies (IIM) (polymyositis (PM), dermatomyosistis (DM), inclusion body myositis (IBM) and juvenile DM (JDM)) and to compare these with healthy controls. <h3>Methods</h3> Serum samples from 149 patients with IIM and 290 healthy controls matched for gender and the month of blood sampling were analysed for 25(OH) vitamin D. ORs for vitamin D classes with 95% CI were calculated using a matched (conditional) logistic regression model. Groups were compared by the Kruskal–Wallis test and p values &lt;0.05 were considered significant. <h3>Results</h3> Patients with IIM had significantly lower serum levels of 25(OH) vitamin D than healthy controls (median 39 (10–168) nmol/l vs 68 (19–197) nmol/l; p=0.0001). There was no significant difference in vitamin D levels between the myositis subgroups. When vitamin D levels were subclassified into deficient (&lt;50 nmol/l), insufficient (50–74 nmol/l) and normal (≥75 nmol/l), most of the patients with PM (68%), DM (65%) and IBM (53%) had deficient levels compared with only 60 (21%) healthy individuals. In patients with IIM the OR for deficient versus normal was 17.7 (95% CI 8.1 to 38.6) and the OR for insufficient versus normal was 2.4 (95% CI 1.2 to 4.7). <h3>Conclusions</h3> Low serum levels of vitamin D were found in most patients with IIM and may confer a risk factor for developing adult myositis, similar to some other autoimmune diseases.
THE EFFECT OF ANTIBACTERIAL DRUGS ON THE FECAL FLORA OF MICE
Authors: Rene Dubos, Russell W. Schaedler, Mallory Stephens
Journal: The Journal of Experimental Medicine (1963)

Oral administration of penicillin, terramycin, or chloramphenicol to NCS mice rapidly brought about profound changes in their fecal flora. The lactobacilli disappeared completely, whereas the numbers of enterococci and Gram-negative bacilli reached very high levels. In contrast, no effect on the fecal flora could be detected following administration of isoniazid in any amount. The intensity and duration of the effects on the fecal flora were related to the type of drug and to the amount of it administered. Chloramphenicol produced disturbances which were less profound and of shorter duration than those produced by penicillin or terramycin. The duration of the disturbances in the fecal flora produced by antibacterial drugs was markedly conditioned by the nutritional regimen. The fecal flora returned to its pretreatment state (large numbers of lactobacilli, few enterococci, and few Gram-negative bacilli) within less than 4 weeks after discontinuing the drug when the mice were fed a complex diet of ill defined composition (commercial pellets). Contrariwise, the fecal flora remained markedly different from that of control mice when the animals were fed semisynthetic diets containing as source of protein either 15 per cent casein or 15 per cent wheat gluten (both supplemented with cystine); or 15 per cent wheat gluten supplemented with lysine, threonine, and cystine. The fecal flora of mice treated with penicillin contained large numbers of lactose-fermenting Gram-negative bacilli, not found in the untreated animals. These lactose fermenters persisted for several months after discontinuance of the drug in mice fed either the casein or gluten diets, but they disappeared rapidly from mice fed pellets. Similar results, although less striking, were obtained with Swiss mice from colonies maintained under usual conditions, and therefore having a fecal flora more complex than that of NCS mice.
Human Brain Capillary Endothelium
Authors: Ye Chen, Richard M. McCarron, Yukoh Ohara, Joliet Bembry, Nabil Azzam, Fred A. Lenz, Esther Shohami, Raphael Mechoulam, Maria Spatz
Journal: Circulation Research (2000)

Abstract —In brain, the regulatory mechanism of the endothelial reactivity to nitric oxide and endothelin-1 may involve Ca 2+ , cytoskeleton, and vasodilator-stimulated phosphoprotein changes mediated by the cGMP/cGMP kinase system. 1 Endothelium of human brain capillaries or microvessels is used to examine the interplay of endothelin-1 with the putative vasorelaxant 2-arachidonoyl glycerol, an endogenous cannabimimetic derivative of arachidonic acid. This study demonstrates that 2-arachidonoyl glycerol counteracts Ca 2+ mobilization and cytoskeleton rearrangement induced by endothelin-1. This event is independent of nitric oxide, cyclooxygenase, and lipoxygenase and is mediated in part by cannabimimetic CB1 receptor, G protein, phosphoinositol signal transduction pathway, and Ca 2+ -activated K + channels. The induced rearrangements of cellular cytoskeleton (actin or vimentin) are partly prevented by inhibition of protein kinase C or high levels of potassium chloride. The 2-arachidonoyl glycerol–induced phosphorylation of vasodilator-stimulated phosphoprotein is mediated by cAMP. These findings suggest that 2-arachidonoyl glycerol may contribute to the regulation of cerebral capillary and microvascular function.
Osteosarcoma: The Addition of Muramyl Tripeptide to Chemotherapy Improves Overall Survival—A Report From the Children's Oncology Group
Authors: Paul A. Meyers, Cindy L. Schwartz, Mark D. Krailo, John H. Healey, Mark L. Bernstein, Donna Betcher, William S. Ferguson, Mark C. Gebhardt, Allen M. Goorin, Michael Harris, Eugenie Kleinerman, Michael P. Link, Helen Nadel, Michael Nieder, Gene P. Siegal, Michael A. Weiner, Robert J. Wells, Richard B. Womer, Holcombe E. Grier
Journal: Journal of Clinical Oncology (2008)

To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma.Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design. The primary end points for analysis were EFS and overall survival.In the current analysis, there was no evidence of interaction, and we were able to examine each intervention separately. The chemotherapy regimens resulted in similar EFS and overall survival. There was a trend toward better EFS with the addition of MTP (P = .08). The addition of MTP to chemotherapy improved 6-year overall survival from 70% to 78% (P = .03). The hazard ratio for overall survival with the addition of MTP was 0.71 (95% CI, 0.52 to 0.96).The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma. The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS.
Feedback inhibition of immunoglobulin gene rearrangement by membrane mu, but not by secreted mu heavy chains.
Authors: J Manz, K Denis, O Witte, R Brinster, U Storb
Journal: The Journal of Experimental Medicine (1988)

Previous work (6-10) has shown that allelic exclusion of Ig gene expression is controlled by functionally rearranged mu and kappa genes. This report deals with the comparison of membrane mu (micron) and secreted mu (microsecond) in promoting such feedback inhibition. Splenic B cell hybridomas were analyzed from transgenic mice harboring a rearranged kappa gene alone or in combination with either an intact rearranged mu gene or a truncated version of the mu gene. The intact mu gene is capable of producing both membrane and secreted forms of the protein, while the truncated version can only encode the secreted form. The role of the microsecond was also tested in pre-B cell lines. Analysis of the extent of endogenous Ig gene rearrangement revealed that (a) the production of micron together with kappa can terminate Ig gene rearrangement; (b) microsecond with kappa does not have this feedback effect; (c) microsecond may interfere with the effect of micron and kappa; and (d) the feedback shown here probably represents a complete shutoff of the specific recombinase by micron + kappa; the data do not address the question of mu alone affecting the accessibility of H genes for rearrangement.
Mutated in colorectal cancer (MCC) is a novel oncogene in B lymphocytes
Authors: Shanique KE Edwards, Jacqueline Baron, Carissa R Moore, Yan Liu, David H Perlman, Ronald P Hart, Ping Xie
Journal: Journal of Hematology & Oncology (2014)

Identification of novel genetic risk factors is imperative for a better understanding of B lymphomagenesis and for the development of novel therapeutic strategies. TRAF3, a critical regulator of B cell survival, was recently recognized as a tumor suppressor gene in B lymphocytes. The present study aimed to identify novel oncogenes involved in malignant transformation of TRAF3-deficient B cells. We used microarray analysis to identify genes differentially expressed in TRAF3−/− mouse splenic B lymphomas. We employed lentiviral vector-mediated knockdown or overexpression to manipulate gene expression in human multiple myeloma (MM) cell lines. We analyzed cell apoptosis and proliferation using flow cytometry, and performed biochemical studies to investigate signaling mechanisms. To delineate protein-protein interactions, we applied affinity purification followed by mass spectrometry-based sequencing. We identified mutated in colorectal cancer (MCC) as a gene strikingly up-regulated in TRAF3-deficient mouse B lymphomas and human MM cell lines. Aberrant up-regulation of MCC also occurs in a variety of primary human B cell malignancies, including non-Hodgkin lymphoma (NHL) and MM. In contrast, MCC expression was not detected in normal or premalignant TRAF3−/− B cells even after treatment with B cell stimuli, suggesting that aberrant up-regulation of MCC is specifically associated with malignant transformation of B cells. In elucidating the functional roles of MCC in malignant B cells, we found that lentiviral shRNA vector-mediated knockdown of MCC induced apoptosis and inhibited proliferation in human MM cells. Experiments of knockdown and overexpression of MCC allowed us to identify several downstream targets of MCC in human MM cells, including phospho-ERK, c-Myc, p27, cyclin B1, Mcl-1, caspases 8 and 3. Furthermore, we identified 365 proteins (including 326 novel MCC-interactors) in the MCC interactome, among which PARP1 and PHB2 were two hubs of MCC signaling pathways in human MM cells. Our results indicate that in sharp contrast to its tumor suppressive role in colorectal cancer, MCC functions as an oncogene in B cells. Our findings suggest that MCC may serve as a diagnostic marker and therapeutic target in B cell malignancies, including NHL and MM.
Clinical Benefit Associated With Idiotypic Vaccination in Patients With Follicular Lymphoma
Authors: Susana Inogès, Mercedes Rodrìguez-Calvillo, Natalia Zabalegui, Ascensiòn Lòpez-Dìaz de Cerio, Helena Villanueva, Elena Soria, Lilia Suárez, Arancha Rodríguez-Caballero, Fernando Pastor, Ricardo García-Muñóz, Carlos Panizo, Javier Pèrez-Calvo, Ignacio Melero, Eduardo Rocha, Alberto Orfao, Maurizio Bendandi
Journal: JNCI Journal of the National Cancer Institute (2006)

Follicular lymphoma is considered incurable, although cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy can induce sequential remissions. A patient's second complete response is typically shorter than that patient's first complete response. Idiotype vaccines can elicit specific immune responses and molecular remissions in patients with follicular lymphoma. However, a clinical benefit has never been formally proven.Thirty-three consecutive follicular lymphoma patients in first relapse received six monthly cycles of CHOP-like chemotherapy. Patients who achieved a second complete response were vaccinated periodically for more than 2 years with autologous lymphoma-derived idiotype protein vaccine. Specific humoral and cellular responses were assessed, and patients were followed for disease recurrence. Statistical tests were two-sided.Idiotype vaccine could be produced for 25 patients who had a second complete response. In 20 patients (80%), a humoral (13/20) and/or a cellular (18/20) idiotype-specific response was detected. The median duration of the second complete response has not been reached, but it exceeds 33 months (range = 20+ to 51+ months). None of the 20 responders relapsed while undergoing active vaccination. All responders with enough follow-up for the comparison to be made experienced a second complete response that was statistically significantly (P<.0001) longer than both their first complete response (18 of 18 patients) and than the median duration of a CHOP-induced second complete response, i.e., 13 months (20 of 20 patients). The five nonresponders all had a second complete response that was shorter (median = 10 months; range = 8-13 months) than their first complete response (median = 17 months; range = 10-39 months).Idiotypic vaccination induced a specific immune response in the majority of patients with follicular lymphoma. Specific immune response was associated with a dramatic and highly statistically significant increase in disease-free survival. This is the first formal demonstration of clinical benefit associated with the use of a human cancer vaccine.
Human Histocompatibility Antigens of Leukocytes
Authors: P I Terasaki, D P Singal
Journal: Annual Review of Medicine (1969)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Macrophages overloaded with tissue debris in Wegener's granulomatosis
Authors: Z Mackiewicz
Journal: Annals of the Rheumatic Diseases (2005)

To analyse some scavenging related molecules in Wegener's granulomatosis (WG) macrophages.Immunohistochemical staining of lung, nasopharynx, and skin for macrophage markers related to scavenging (macrophage scavenger receptor MARCO, collagenase-1 and gelatinase-B), formation of multinuclear foreign body giant cells (ADAM 9/meltrin-gamma and ADAM 12/meltrin-alpha), and cell debris derived from neutrophils, endothelial cells and mast cells (specific granule protein 28 (SGP28), von Willebrand factor (vWF) and mast cell tryptase, respectively). TechMate staining robot and biotin-streptavidin protocol were used.Some macrophages were activated and expressed collagenase-1 and gelatinase-B. Approximately 5% of macrophages expressed scavenger receptor, whereas 20-30% were meltrin positive. Interstitial and granuloma associated macrophages and giant cells contained partly undigested, immunoreactive SGP28-, vWF- and tryptase-positive cell rests and collagenous matrix. Lymphocytic follicles with germinal centres were found in the same areas.In WG tissue lesions macrophage and giant cells seem to be overwhelmed by the bulk to be scavenged. Despite cellular activation and continuing maturation to professional scavenger receptor (MARCO) and meltrin positive multinuclear giant cells combined with an organisation into granulomas, macrophages still contain partially undigested cell and tissue rests. This necrotic and damaged self may be the driving force for the formation of giant cell ("foreign body") granulomas. This, together with the local formation of secondary lymphatic follicles (with germinal centres), indicates active local antigen processing and presentation.
Tubular aggregate myopathy presenting with acute type II respiratory failure and severe orthopnoea
Authors: N Shahrizaila
Journal: Thorax (2005)

Acute hypercapnic respiratory failure (AHRF) is a common reason for hospital admission. Most patients have an underlying chronic lung disease such as chronic obstructive pulmonary disease. We report the case of a man who presented with AHRF secondary to tubular aggregate myopathy.
Outdoor air pollution, climatic changes and allergic bronchial asthma
Authors: G. D'Amato, G. Liccardi, M. D'Amato, M. Cazzola
Journal: European Respiratory Journal (2002)

Both the prevalence and severity of respiratory allergic diseases such as bronchial asthma have increased in recent years. Among the factors implicated in this “epidemic” are indoor and outdoor airborne pollutants. Urbanisation with its high levels of vehicle emissions and Westernised lifestyle parallels the increase in respiratory allergy in most industrialised countries, and people who live in urban areas tend to be more affected by the disease than those of rural areas. In atopic subjects, exposure to air pollution increases airway responsiveness to aeroallergens. Pollen is a good model with which to study the interrelationship between air pollution and respiratory allergic diseases. Biological aerosols carrying antigenic proteins, such as pollen grains or plant-derived paucimicronic components, can produce allergic symptoms. By adhering to the surface of these airborne allergenic agents, air pollutants could modify their antigenic properties. Several factors influence this interaction, i.e. , type of air pollutant, plant species, nutrient balance, climatic factors, degree of airway sensitisation and hyperresponsiveness of exposed subjects. However, the airway mucosal damage and the impaired mucociliary clearance induced by air pollution may facilitate the penetration and the access of inhaled allergens to the cells of the immune system, and so promote airway sensitisation. As a consequence, an enhanced immunoglobulin E-mediated response to aeroallergens and enhanced airway inflammation favoured by air pollution could account for the increasing prevalence of allergic respiratory diseases in urban areas.
Effects of fenoterol on ventilatory responses to hypoxia and hypercapnia in normal subjects.
Authors: Y Yoshiike, S Suzuki, Y Watanuki, T Okubo
Journal: Thorax (1995)

BACKGROUND--The effects of beta 2 adrenergic agonists on chemoreceptors remain controversial. This study was designed to examine whether fenoterol, a beta 2 adrenergic agonist, increases the ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) in normal subjects. METHODS--HCVR was tested with a rebreathing method and HVR was examined with a progressive isocapnic hypoxic method in 11 normal subjects. Both HCVR and HVR were assessed by the slope of occlusion pressure (P0.1) or ventilation (VE) plotted against end tidal carbon dioxide pressure and arterial oxygen saturation, respectively. Respiratory muscle strength, spirometric values and lung volume were measured. After a single oral administration of 5 mg fenoterol or placebo HCVR and HVR were evaluated. RESULTS--Fenoterol treatment did not change the specific airway conductance or forced expiratory volume in one second. Respiratory muscle strength did not change. Fenoterol increased the slope of the HCVR of both P0.1 (from 0.251 (0.116) to 0.386 (0.206) kPa/kPa, average increase 71%) and VE (from 10.7 (3.4) to 15.1 (4.2) l/min/kPa, average increase 52%), and shifted the response curves to higher values. For the HVR fenoterol increased the slopes of both P0.1 and VE (from -4.06 (2.00) x 10(-3) to -7.99 (4.29) x 10(-3) kPa/%, an average increase of 83%, and from -0.221 (0.070) to -0.313 (0.112) l/min/%, a 44.5% increase, respectively), and shifted the response curves to higher values. CONCLUSION--Acute administration of fenoterol increases the ventilatory responses to both hypercapnia and hypoxia in normal subjects.
The Chemical Theory of Contagium compared with the Corpuscular Theory, with Special Reference to the Action of Disinfectants
Authors: J. L. Notter
Journal: BMJ (1878)

J41ly pt0j18784TNRW 24iIf JjWWWAL ~1-URNdL.ñothing abnormal in the vessels or grey s.4ttp.the -peripheral layer of white matter was scarcely tinted; there.was: overgrowth of connec- tive tissue and atrophy of nerve-fibres.Below this, the grey cornua had lost their symmetry; in one section,, the, right posterior cornm was atrophied, while in several others, again, Iplow this, the left anterior horn was shortened, and a portion of thecentral grey mass was en- croached upon by a tract of lighter colouVed tissue distinguishable to the naked eye, passing obliquely backwards.The central canal was replaced by proliferated nuclei, and appeared as if pushed towards the