tbuckley/cabot-search huggingface dataset:
Chronic bronchitis sub-phenotype within COPD: inflammation in sputum and biopsies
Authors: J. B. Snoeck-Stroband, T. S. Lapperre, M. M. E. Gosman, H. M. Boezen, W. Timens, N. H. T. ten Hacken, J. K. Sont, P. J. Sterk, P. S. Hiemstra
Journal: European Respiratory Journal (2007)

The presence of chronic bronchitis predicts a more rapid decline of forced expiratory volume in one second (FEV 1 ) in patients with chronic obstructive pulmonary disease (COPD). The hallmark of COPD is airway inflammation. It was hypothesised that COPD patients with chronic bronchitis are characterised by a distinct inflammatory cell profile, as measured in bronchial biopsies and sputum. From 114 COPD patients (male/female ratio 99/15, mean± sd age 62±8 yrs, current smoking 63%, post-bronchodilator FEV 1 63±9% predicted, no steroids), with and without chronic bronchitis, inflammatory cell counts in bronchial biopsies and induced sputum were measured. Analysis was carried out by logistic regression. COPD patients with chronic bronchitis had lower eosinophil counts in biopsies and higher percentages of sputum eosinophils than patients without those symptoms, which remained after adjustment for smoking and sex. Patients with chronic bronchitis also showed higher percentages of macrophages and lower percentages of neutrophils in sputum, which could be explained by differences in smoking and sex. It was concluded that chronic bronchitis reflects an inflammatory sub-phenotype among patients with chronic obstructive pulmonary disease. The present results indicate a preferential distribution of eosinophils towards the airway lumen in patients with chronic bronchitis. This may have implications for anti-inflammatory treatment of chronic obstructive pulmonary disease patients with chronic bronchitis.
Relationship between Expression of Bcl-2 Genes and Growth Factors in Ischemic Acute Renal Failure in the Rat
Authors: GLENDA GOBÉ, XIAO-JU ZHANG, DESLEY A. WILLGOSS, ESTELLE SCHOCH, NICOLE A. HOGG, ZOLTÁN H. ENDRE
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The promotion of cell survival and regeneration in acute renal failure (ARF) is important for restitution of renal function. This study analyzes the temporal and spatial relationship between expression of pro- and anti-apoptotic members of the Bcl-2 gene family (Bcl-2, Bcl-X L , Bax) and epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β), growth factors that are thought to be reparative in ARF. A rat model of ischemic ARF involving 30 min of bilateral renal artery occlusion followed by reperfusion for 0 to 14 d was used. Apoptosis and mitosis were quantified and qualitative assessment was made of other cellular damage including necrosis and loss of cellular adhesion. Locality and level of expression of the Bcl-2 and growth factor proteins were determined using immunohistochemistry. Apoptosis peaked between 4 and 14 d postischemia in both proximal and distal tubules. Mitosis peaked at 2 d in proximal tubules and 4 to 14 in the distal tubules. A spatio-temporal relationship was observed between anti-apoptotic Bcl-2 gene family members and growth factors after ischemia-reperfusion. In control kidneys, expression of Bcl-2, Bcl-X L was low in epithelium of distal tubules, Bax had low-to-moderate expression in the proximal tubule and had low expression in the distal tubule, EGF and IGF-1 had low-to-moderate expression in the distal tubule, and TGF-β had low expression in the proximal tubule. In contrast, within 24 h of reperfusion, distal tubules showed a marked increase in expression of Bcl-2 and a moderate increase in Bcl-X L and Bax. Proximal tubules showed a marked increase in Bax expression and a moderate increase in Bcl-X L . Twenty-four hours after expression of the Bcl-2 proteins was increased, IGF-1 and EGF protein levels were increased in the distal tubule, similar to the Bcl-2 anti-apoptotic proteins, and were also detected in the adjacent proximal tubules, suggestive of paracrine action in these tubules. TGF-β expression was moderately increased in regenerating proximal tubules, but no relationship was seen with the pattern of expression of the Bcl-2 genes. An explanation of these results is that the distal tubule is adaptively resistant to ischemic injury via promotion of survival by anti-apoptotic Bcl-2 genes, and its survival allows expression of growth factors critical not only to the maintenance and regeneration of its own cell population (autocrine action), but also to the adjacent ischemia-sensitive proximal tubular cells (paracrine action).
Endotoxin-induced plasma exudation in guinea-pig airways in vivo and the effect of neutrophil depletion
Authors: TW Evans, DF Rogers, MG Belvisi, JA Rohde, KF Chung, PJ Barnes
Journal: European Respiratory Journal (1990)

The contribution of neutrophils to the action of endotoxin on plasma exudation in the airways of anaesthetized guinea-pigs was quantified by measuring the extravasation of Evans blue dye. Endotoxin (Salmonella enteritidis) caused a dose-dependent increase in microvascular leakage to Evans blue dye which was maximal after 25 min (p less than 0.05). The minimum dose tested that induced a significant rise in leakage was 1.5 mg.kg-1 for "central" intrapulmonary airways (ipa); 4.5 mg.kg-1 for trachea and main bronchi and 7.5 mg.kg-1 for nasal mucosa, larynx and "peripheral" ipa. Depletion of circulating neutrophil numbers by 97% using an antibody to guinea-pig neutrophils caused no significant diminution of the effects of endotoxin on leakage in any part of the airway. There was no significant influx of neutrophils into the airway interstitium at the time of maximum extravasation of Evans blue. We conclude that endotoxin-induced airway microvascular permeability is dependent upon mechanisms other than circulating neutrophils.
Cell based therapy in Parkinsonism
Authors: Johannes PJM de Munter, Chongsik Lee, Erik Ch Wolters
Journal: Translational Neurodegeneration (2013)

Parkinson's disease (PD) is a synucleinopathy-induced chronic progressive neurodegenerative disorder, worldwide affecting about 5 million humans. As of yet, actual therapies are symptomatic, and neuroprotective strategies are an unmet need. Due to their capability to transdifferentiate, to immune modulate and to increase neuroplasticity by producing neurotrophic factors, adult stem cells (ASC) might fill this gap. Preclinical research in 6-hydroxydopamine (6-OHDA) and/or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned animals established persistent improvements of motor behavior after ASC-treatment. Histological/histochemical measurements in these animals evidenced an intracerebral applied ASC-induced increase of Tyrosine Hydroxylase-positive (TH+) cells with increased striatal dopamine levels, suggesting cell rescue. Likewise, clinical experience with subventricular applied ASCs in PD patients, although limited, is encouraging, evidencing neurorescue especially during the early phase of the disease. In multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) patients, though, only marginal reduced progression of natural progression could be established after subventricular or intravasal ASC implantations.
Neutral Lipid from Proteinuric Rat Urine Is a Novel Inhibitor of the Red Blood Cell Calcium Pump
Authors: ARMANDO LINDNER, THOMAS R. HINDS, ALISON JOLY, GEORGE F. SCHREINER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Proteinuria may be associated with hypertension and progression of renal insufficiency, which in turn may accompany abnormalities in cell calcium homeostasis. Therefore, urine from rats made proteinuric by puromycin aminoglycoside administration was analyzed, in a search for factors affecting cellular calcium transport. Proteinuric urine was fractionated by thin-layer chromatography and HPLC, and the effects of the fractions on the plasma membrane calcium pump in human red blood cells were assessed. Proteinuric urine contained a powerful specific inhibitor of the calcium pump that had little or no effect on the Na + /K + - or Mg 2+ -ATPases. The inhibitor was characterized as a neutral lipid, migrating as a single band, that inhibited 45 Ca 2+ efflux. To confirm the presence of an inhibitor in other proteinuric states, the urine from two patients with proteinuria was examined and subjected to chromatography as in the rat studies. These thin-layer chromatographic fractions contained a very strong inhibitor of the red blood cell calcium pump, suggesting that this substance may have relevance for the pathogenesis of proteinuric renal disease in human patients. Rat proximal tubule cells in tissue culture, when challenged with lipid-replete albumin, secreted an inhibitor of the calcium pump that migrated in the same chromatographic band as the urine factor. Therefore, the processing of fatty acids borne by albumin into endocytosing proximal tubular epithelium results in the synthesis and release of a previously unknown lipid modulator of the calcium pump, an effect that may predispose kidney tissue toward elevations in cytosolic calcium levels in target cells.
Drugs modulating the biological effects of peroxynitrite and related nitrogen species
Authors: Ana Olmos, Rosa M. Giner, Salvador Máñez
Journal: Medicinal Research Reviews (2006)

Abstract The term “reactive nitrogen species” includes nitrogen monoxide, commonly called nitric oxide, and some other remarkable chemical entities (peroxynitrite, nitrosoperoxycarbonate, etc.) formed mostly from nitrogen monoxide itself in biological environments. Regardless of the specific mechanisms implicated in their effects, however, it is clear that an integrated pharmacological approach to peroxynitrite and related species is only just beginning to take shape. The array of affected chemical and pathological processes is extremely broad. One of the most conspicuous mechanisms observed thus far has been the scavenging of the peroxynitrite anion by molecules endowed with antioxidant activity. This discovery has in turn lent great significance to several naturally occurring and synthetic antioxidants, which usually protect not only against oxidative reactions, but also from nitrating ones, both in vitro and in vivo . This has proven to be beneficial in different tissues, especially within the central nervous system. Taking these results and those of other biochemical investigations into account, many research lines are currently in progress to establish the true potential of reactive nitrogen species deactivators in the therapy of neurological diseases, ischemia‐reperfusion damage, renal failure, and lung injury, among others. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 1, 1–64, 2007
Rituximab in CD20 positive multiple myeloma
Authors: P Moreau, L Voillat, L Benboukher, C Mathiot, C Dumontet, N Robillard, O Hérault, F Garnache, R Garand, N Varoqueaux, H Avet-Loiseau, J L Harousseau, R Bataille
Journal: Leukemia (2007)
Endothelial Nitric Oxide Synthase Regulates Microlymphatic Flow via Collecting Lymphatics
Authors: Jeroen Hagendoorn, Timothy P. Padera, Satoshi Kashiwagi, Naohide Isaka, Fatima Noda, Michelle I. Lin, Paul L. Huang, William C. Sessa, Dai Fukumura, Rakesh K. Jain
Journal: Circulation Research (2004)

Functional interactions between the initial and collecting lymphatics, as well as the molecular players involved, remain elusive. In this study, we assessed the influence of nitric oxide (NO) on lymphatic fluid velocity and flow, using a mouse tail model that permits intravital microscopy and microlymphangiography. We found that NO synthase (NOS) inhibition decreased lymphatic fluid velocity in the initial lymphatics, without any effect on their morphology. Using the same model, we found a similar effect in eNOS-/- mice and in mice treated with a selective endothelial NOS (eNOS) inhibitor. Next, we uncoupled the superficial initial lymphatics from the deeper collecting lymphatics by ligating the latter and found that lymphatic fluid velocity in NOS-inhibited mice became equal to that in control animals. Surprisingly, lymphatic fluid velocity was significantly increased after ligating the collecting lymphatics, and there was a concomitant increase in injection rate and mean lymphatic vessel diameter. Our results provide the first in vivo evidence that eNOS affects function of the whole microlymphatic system and that it is regulated via the collecting lymphatics.
Decision aids that really promote shared decision making: the pace quickens
Authors: Thomas Agoritsas, Anja Fog Heen, Linn Brandt, Pablo Alonso-Coello, Annette Kristiansen, Elie A Akl, Ignacio Neumann, Kari AO Tikkinen, Trudy van der Weijden, Glyn Elwyn, Victor M Montori, Gordon H Guyatt, Per Olav Vandvik
Journal: BMJ (2015)

Decision aids can help shared decision making, but most have been hard to produce, onerous to update, and are not being used widely. <b>Thomas Agoritsas and colleagues</b> explore why and describe a new electronic model that holds promise of being more useful for clinicians and patients to use together at the point of care
Osteonecrosis of the Tibia Associated With Imatinib in Metastatic GI Stromal Tumor
Authors: Chun-Nan Yeh, Chen-Ju Fu, Tzu-Chen Yen, Kun-Chun Chiang, Yi-Yin Jan, Miin-Fu Chen
Journal: Journal of Clinical Oncology (2013)

Case ReportAn abdominal mass was incidentally found by abdominal echography in a 61-year-old otherwise healthy woman during a routine physical checkup in December 2010.Subsequent abdominal computed tomography (CT) revealed a multilobulated heterogeneously enhanced mass measuring 8.2 ϫ 5.6 cm in the lower abdomen with several nodules of various sizes in the peritoneum, suggesting peritoneal seeding.Multiple nodules with ring enhancement were detected in both lobes of the liver, suggesting metastasis.In addition, needle biopsy of the liver and histologic examination of the biopsied specimen revealed spindle cell tumor with positive immunostaining of CD117, confirming the diagnosis of metastatic GI stromal tumor (GIST).Tumor DNA amplified by polymerase chain reaction revealed a c-kit mutation consisting of a deletion mutation at codons 553 to 558 in exon 11.The patient received therapy with four 100-mg capsules of imatinib daily in January 2011.After 3 months of treatment, partial re-e248
Neurobiology of Aggression and Violence
Authors: Larry J. Siever
Journal: American Journal of Psychiatry (2008)

Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of “top-down” control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of “top-down” control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance “top-down” control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic.
Simultaneous Disruption of Interleukin (IL)-4 and IL-13 Defines Individual Roles in T Helper Cell Type 2–mediated Responses
Authors: Grahame J. McKenzie, Padraic G. Fallon, Claire L. Emson, Richard K. Grencis, Andrew N.J. McKenzie
Journal: The Journal of Experimental Medicine (1999)

Using a single vector targeting strategy, we have generated mice with a combined deficiency of interleukin (IL)-4 and IL-13 to clarify their roles in T helper type 2 (Th2) cell responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of the double-deficient mice with those generated by wild-type, IL-4-deficient, and IL-13-deficient mice. Using a pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that although eosinophil infiltration, immunoglobulin E, and IL-5 production are reduced in the IL-4-deficient mice and IL-13-deficient mice, they are abolished only in the combined absence of both cytokines. Furthermore, IL-4/13-deficient animals are severely impaired in their ability to expel the gastrointestinal nematode Nippostrongylus brasiliensis. Unexpectedly, N. brasiliensis-infected IL-4/13-deficient mice developed elevated IL-5 and eosinophilia, indicating that compensatory mechanisms exist for the expression of IL-5, although serum IgE remained undetectable. IL-4/13-deficient mice default to a Th1-like phenotype characterized by the expression of interferon gamma and the production of IgG2a and IgG2b. We conclude that IL-4 and IL-13 cooperate to initiate rapid Th2 cell-driven responses, and that although their functions overlap, they perform additive roles.
Trends in the first decade of 21st century healthcare utilisation in a rheumatoid arthritis cohort compared with the general population
Authors: Sofia Hagel, Ingemar F Petersson, Ann Bremander, Elisabet Lindqvist, Charlotte Bergknut, Martin Englund
Journal: Annals of the Rheumatic Diseases (2012)

Purpose To study 21st century trends in healthcare utilisation by patients with rheumatoid arthritis (RA) compared with the general population. Methods Observational cohort study. Using Swedish healthcare register data, we identified 3977 Region Skåne residents (mean age in 2001, 62.7 years; 73% women) presenting with RA (International Classification of Diseases-10 codes M05 or M06) in 1998–2001. We randomly sampled two referents from the general population per RA patient matched for age, sex and area of residence. We calculated the year 2001–2010 trends for the annual ratio (RA cohort/referents) of the mean number of hospitalisations and outpatient clinic visits. Results By the end of the 10-year period, 62% of patients and 74% of referents were still alive and resident in the region. From 2001 to 2010, the ratio (RA cohort/referents) of the mean number of hospitalisations for men and women decreased by 27% (p=0.01) and 28% (p=0.004), respectively. The corresponding decrease was 29% (p=0.005) and 16% (p=0.004) for outpatient physician care, 34% (p=0.009) and 18% (p=0.01) for nurse visits, and 34% (p=0.01) and 28% (p=0.004) for physiotherapy. The absolute reduction in number of hospitalisations was from an annual mean of 0.79 to 0.69 in male patients and from 0.71 to 0.59 in female patients. The corresponding annual mean number of consultations in outpatient physician care by male and female RA patients changed from 9.2 to 7.7 and from 9.9 to 8.7, respectively. Conclusions During the first decade of the 21st century, coinciding with increasing use of earlier and more active RA treatment including biological treatment, overall inpatient and outpatient healthcare utilisation by a cohort of patients with RA decreased relative to the general population.
Initial results with recombinant interferon alfa-2b in patients with chronic hepatitis C: the United States experience.
Authors: G L Davis
Journal: Gut (1993)

Early experience with recombinant interferon alfa-2b in chronic hepatitis C (HCV) has shown that normalisation of serum alanine aminotransferase activities and reduction in hepatic inflammation can be achieved in about 40% of patients. This occurs with loss of viral replication as measured by polymerase chain reaction for HCV-RNA. Further studies are needed to identify patients most likely to respond to treatment and to investigate the issues of non-response and relapse when treatment is stopped. Alternative interferon treatment regimens, as well as other drugs and combinations of agents, need to be investigated.
Mediastinal emphysema: aetiology, diagnosis, and treatment.
Authors: J M Gray, G C Hanson
Journal: Thorax (1966)

Mediastinal emphysema is a condition frequently omitted in the differential diagnosis of retrosternal chest pain; it is generally benign but on occasions can be fatal.Little has been written about this condition, and, although rare, it has probably been misdiagnosed or has not been detected in the past.
Nuclear receptor Nur77 inhibits vascular outward remodelling and reduces macrophage accumulation and matrix metalloproteinase levels
Authors: Peter I. Bonta, Hanke L. Matlung, Mariska Vos, Stephan L.M. Peters, Hans Pannekoek, Erik N.T.P. Bakker, Carlie J.M. de Vries
Journal: Cardiovascular Research (2010)

Structural adaptation of the vessel wall in response to sustained alterations in haemodynamic forces is known as vascular remodelling. Detailed knowledge on the mechanism underlying this vascular response is limited, and we aimed to study the function of Nur77 in smooth muscle cells (SMCs) in arterial remodelling. Carotid artery ligation in mice results in flow-induced, outward remodelling of the contralateral carotid artery, and we observed enhanced Nur77 expression during this process. Transgenic mice that express Nur77 or its dominant-negative variant, denoted as 'ΔTA' in arterial SMCs, were exposed to carotid artery ligation, and after 4 weeks pressure–diameter relationships were measured. Structural outward remodelling is inhibited in Nur77-transgenic mice when compared with wild-type and ΔTA-transgenic mice. The key determinants of remodelling vascular tone and macrophage accumulation were studied. No difference in contractile and relaxant responses was detected in isolated aorta, carotid, and mesenteric artery segments between transgenic and wild-type mice. SMC-specific overexpression of Nur77 in transgenic mice reduced macrophage accumulation and repressed matrix metalloproteinase (MMP)1 and MMP9 expression at early time points. MMP2 protein expression was reduced in Nur77-transgenic mice, whereas in ΔTA-transgenic mice MMP2 expression was increased. Nur77 is induced during outward remodelling and inhibits this vascular adaptation in mice. Nur77-mediated inhibition of arterial remodelling involves a reduction in both macrophage accumulation and MMP expression levels.
The Internal Distribution of Hydrogen Ions With Varying Degrees of Metabolic Acidosis1
Authors: William B. Schwartz, Karl J. Ørning, Richard Porter
Journal: Journal of Clinical Investigation (1957)

When a mineral acid is administered to animal or man, a substantial fraction is buffered in sites other than blood or interstitial fluid.Van Slyke and Cullen (1) first observed that total blood vol- ume could account for the buffering of only onesixth of a mineral acid load and suggested that buffer substances throughout the body, including those of the tissues, are utilized in the defense against metabolic acidosis.Recent studies in sev- eral laboratories have provided more detailed quantitative data on the internal distribution of administered hydrogen ions.Swan and Pitts (2) in nephrectomized dogs and Schwartz, Jenson, and Relman (3) in normal human subjects have dem- onstrated that only about one-half of a mineral acid load is buffered in the extracellular space and red blood cells.The remaining hydrogen ions exchange with sodium and potassium from tissue and bone and are presumably buffered in these areas.