tbuckley/cabot-search huggingface dataset:
A randomized <scp>DBPC</scp> trial to determine the optimal effective and safe dose of a <scp>SLIT</scp>‐birch pollen extract for the treatment of allergic rhinitis: results of a phase <scp>II</scp> study
Authors: O. Pfaar, E. van Twuijver, J. D. Boot, D. J. E. Opstelten, L. Klimek, R. van Ree, Z. Diamant, P. Kuna, P. Panzner
Journal: Allergy (2015)

Sublingual immunotherapy (SLIT) is a potential efficacious and safe treatment option for patients with respiratory, IgE-mediated allergic diseases. A combined tolerability, dose-finding study with a sublingual liquid birch pollen preparation (SB) was conducted.Two hundred and sixty-nine adults with birch-pollen-induced AR were randomized to placebo, SB: 3333, 10,000, 20,000 or 40,000 AUN/ml. Differences in symptom scores following a titrated nasal provocation test (TNPT) at baseline and after 5 months of treatment were determined. Safety, tolerability, birch-pollen-specific immunoglobulin levels and peak nasal inspiratory flow (PNIF) were also measured (all measures determined outside the birch pollen season).In all treatment groups, an improvement in symptom scores after treatment compared to baseline was observed, with an additional stepwise improvement in the active groups compared to placebo, which was significant in high-dose groups (P = 0.008 and P < 0.001, respectively). For this primary endpoint, a significant linear dose-response curve was observed: the higher the dose, the better the improvement observed. Likewise, active treatment resulted in an increase in PNIF and serum IgG levels compared to placebo. The highest improvements were found in the 40,000 AUN/ml group. All active dosages resulted in more adverse reactions than placebo, which were mainly mild and well-controlled.A multicentre trial evaluated the dose-response and tolerability of SB. All active treatment groups showed better responses than placebo for both primary and secondary parameters. The results indicate that, within the studied dose range, SB 40,000 AUN/ml is the most optimal effective and safe dose (ClinicalTrials.gov: NCT01639768).
Purification and Transplantation of Hepatocytes From Livers of Carcinogen-Treated Rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;,&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: S B Miller, T P Pretlow, J A Scott, T G Pretlow
Journal: JNCI Journal of the National Cancer Institute (1982)

Young adult male F344 rats were given 90 ppm diethylnitrosamine in drinking water for 5 weeks. Cells were obtained in suspenslon from the livers of these animals by in situ perfusion of collagenase. Cells were separated in a 2.7-16% (wt/wt) continuous gradient of Ficoll in tissue culture medium in the Sorvall TZ-28 reorienting zonal rotor for 10 minutes at 4°C with a centrifugal force of 12xg at the sample-gradient interface (26xg at the gradient-cushion interface). Up to half a billion liver cells were separated without exceeding the band capacity. In all experiments the purest fractions contained more than 90% hepatocytes. After centrifugation, 72.4±6.6% of the purified hepatocytes had histochemically demonstrable γ-glutamyl transpeptidase (GGT). When purified hepatocytes were injected into the mesenteric veins of rats given a diet containing 0.02% (wt/wt) N-2-fluorenylacetamide for 7 days and subjected to partial hepatectomy, all rats that received these cells developed foci that exhibited histochemically demonstrable GGT. Hepatocytes with histochemically demonstrable GGT make up all or part of what previously has been referred to as “liver colony-forming units.” With the TZ-28 reorienting zonal rotor, these cells can be purified in biochemically preparative quantities.
Infective endocarditis not related to intravenous drug abuse in HIV-1-infected patients: report of eight cases and review of the literature
Authors: J.E. Losa, J.M. Miro, A. Del Rio, A. Moreno-Camacho, F. Garcia, X. Claramonte, F. Marco, C.A. Mestres, M. Azqueta, J.M. Gatell
Journal: Clinical Microbiology and Infection (2003)
Multiplication of Avian Leukosis Virus in Endocrine Organs of Congenitally Infected Chickens&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Henry S. Di Stefano, Robert M. Dougherty
Journal: JNCI Journal of the National Cancer Institute (1969)

Thyroid, parathyroid, pituitary, and adrenal glands from viremic chickens congenitally infected with avian leukosis virus (ALV) were examined with the electron microscope to ascertain whether the epithelial cells supported multiplication of ALV. Virus multiplied in parenchymal cells of the anterior hypophysis, thyroid, parathyroid, and adrenal cortex. No viral buds were found associated with parenchymal cells of the adrenal medulla.
Complications of radiofrequency thermal ablation in hepatocellular carcinoma: what about "explosive" spread?
Authors: C Angonese, A Baldan, U Cillo, A D'Alessandro, M De Antoni, M De Giorgio, A Masotto, D Marino, M Massani, M Mazzucco, E Miola, D Neri, D Paccagnella, G Pivetta, L Tommasi, F Tremolada, A Tufano, G Zanus, F Farinati
Journal: Gut (2006)

measurement in the investigation and diagnosis of gastro-oesophageal reflux disease.
Plasma cytokine levels in non-smoking and smoking patients with COPD
Authors: Anatoli Tahanovich, Aliaksei Kadushkin
Journal: European Respiratory Journal (2014)

Background. The results of recently published studies suggest that there are some molecular differences in the pathogenesis of COPD between smokers and non-smokers.

Aim. The aim of the study was to determine the levels of cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF) and neutrophil elastase (NE) in blood of non-smokers and smokers with COPD.

Methods. We examined 21 non-smokers with COPD, 20 smokers with COPD, 20 healthy non-smokers and 21 healthy smokers. Plasma levels of six inflammatory mediators and protease NE were determined by an immunoassay technique.

Results. Concentrations of IL-8, VEGF and NE were significantly elevated in smokers with COPD compared to healthy smokers, and in non-smoking COPD patients compared to healthy non-smokers. Increased level of TNF-α was observed only in non-smoking COPD patients compared to non-smoking healthy control subjects. Smokers with COPD had higher concentration of NE and lower level of TNF-α than non-smokers with COPD. There were no differences in IL-1β, IL-6 and IL-10 levels between the investigated groups. Patients (smokers and non-smokers combined) with high and very high impact level of COPD on health status (according to the results of CAT, COPD Assessment Test) had significantly higher levels of TNF-α and VEGF than patients with low and medium impact level.

Conclusion. Our findings reveal some new molecular differences in the pathogenesis of COPD between non-smokers and smokers.
Abstract 59: A Protective Role Of Adenine Nucleotide Translocator 1 In The Inflammatory Response Following Myocardial Infarction
Authors: Shi Pan, Nadan Wang, Shey-Shing Sheu
Journal: Circulation Research (2014)

Background: Inflammation following myocardial infarction (MI) contributes significantly to the pathogenesis of heart failure. Although the initial stage of inflammatory response is necessary for the repair and healing of myocardium, excessive inflammation post MI causes adverse remodeling leading to heart failure. Recent studies suggest that mitochondrial dysfunction plays an important role in inflammation. However, the molecular target in cardiac mitochondria and the mechanisms of action remain unclear. We hypothesized that mitochondrial ADP/ATP carrier adenine nucleotide translocator isoform 1 (ANT1) is protective in post MI inflammation. Methods and Results: MI was induced by permanent occlusion of left anterior descending artery in C57BL/6 mice. In the inflamed heart following MI, ANT1 protein levels were significantly decreased in the left ventricle (0.48±8.94%), indicating ANT1 down-regulation occurs in myocardial inflammation following MI. To delineate the mechanisms involved, we performed siRNA knockdown of ANT1 in myocardium-derived H9c2 cells and cardiomyocytes, and examined tumor necrosis factor alpha (TNFα)-induced pro-inflammatory response. Knocking down ANT1 significantly increased the expression of TNFα (~10-fold) and interleukin-6 (IL-6) (~3.6-fold) concomitant with increased reporter gene activity of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) (~61±1.22%) in response to TNFα. These effects were not due to mitochondria loss because no changes were detected for voltage-dependent anion channel, or cyclophilin D when ANT1 is knocked down. Confocal microscopy analysis indicated that ANT1 knockdown increased TNFα-induced donut/blob-shaped mitochondria (~4.9-fold). Interestingly, exogenous TNFα and lipopolysaccharide (LPS) in turn significantly decreased ANT1 protein levels (~37±13%; ~37±6%, respectively) suggesting a feed forward regulation of pro-inflammatory cytokine expression activated by ANT1 down-regulation. Conclusion: These data suggest that cardiac inflammation is dependent on, in part, the function of ANT1. Preventing ANT1 down-regulation can be a novel molecular target to attenuate post MI inflammation and heart failure.
Paco2: a marker of severity in community acquired pneumonia
Authors: P Palchaudhuri
Journal: Thorax (2005)

▴ Sin DD, Man SFP, Thomas J. Marrie TJ. Arterial carbon dioxide tension on admission as a marker of in-hospital mortality in community-acquired pneumonia. Am J Med2005;118:145–50

[OpenUrl][1][PubMed][2]



Arterial carbon dioxide tension (Paco2) has not previously been studied in detail as a predictor of mortality in patients with community acquired pneumonia. This retrospective Canadian study examined the relationship between Paco2 and in-hospital mortality in patients with community acquired pneumonia.

Of the 2171 study subjects, in-hospital mortality (10%) was …

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Munchausen's Syndrome—Masquerading as Necrotizing Fasciitis
Authors: A J Park, G V Scerri
Journal: Journal of the Royal Society of Medicine (1996)

We would like to present a novel form of Munchausen's syndrome which presented us with a difficult problem in the midst of the recent media hysteria regarding flesh eating bacteria. This condition, first described by Richard Asher in 1951 1 , is often very difficult to diagnose and it is not, therefore, surprising that the victims have been through several epsiodes of treatment before the suspicions of staff are raised. It owes its name to a fictitious character, Baron Karl Friedrich Hieronymus Freihess von Munchausen, who recounted extraordinary and wildly exaggerated exploits of adventure and daring, not unlike patients who present with this condition. Our enquiries revealed that the laid down procedure when faced with a patient with this condition is that the regional medical officer (RMO) should be contacted. It is then his responsibility to contact other RMOs, who in turn pass the information on to accident and emergency consultants in their area.
Venous thromboembolism in patients with myelodysplastic syndrome treated with lenalidomide: Incidence and risk factors
Authors: N. A. Brandenburg, L. Weiss, R. Bwire, M. Schmidt, R. Knight, A. F. List
Journal: Journal of Clinical Oncology (2008)

7084 Background: The frequency of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) among patients with myelodysplastic syndrome (MDS) has not been characterized. This analysis describes the frequency of and risk factors for VTE among MDS patients participating in clinical studies of lenalidomide. Methods: Demographic and clinical risk factors for VTE were assessed for 408 patients with a histologically confirmed diagnosis of MDS according to FAB criteria: 45 patients in a single-center, open-label, pilot dose-finding lenalidomide study and 363 patients with low- or intermediate-1-risk MDS without (N=215) or with (N=148) a del (5q) cytogenetic abnormality and red blood cell-transfusion-dependent anemia enrolled in multi-center single-arm open-label studies. Erythropoiesis-stimulating agents were excluded in all studies. Results: VTE occurred in 14 patients during study treatment (11 DVT; 4 PE), resulting in a cumulative incidence for first VTE of 3.4% (≤365 days, 2.9%). Nine patients experienced VTE within 6 months of starting study drug (range 5–590 days; median 112.5 days). There were no differences in median age (68 vs. 72; p = 0.19) or median MDS duration at baseline (1.75 years vs. 2.40; p = 0.37) between patients with and without VTE. No differences in gender, baseline IPSS score, FAB classification, ECOG scores or number of red blood cell units transfused during the 8-week baseline period were observed (p > 0.05, all comparisons). Review of safety information identified recognized risk factors for VTE in 12/14 patients, including hospitalization (n=3), VTE history (n=3), other peripheral vascular disease (n=2), congestive heart failure/atrial fibrillation (n=4), diabetes (n=4), overweight (n=1), stroke (n=1), prior malignancy (n=2), and hormone replacement therapy (n=1). Conclusions: The incidence of VTE among MDS patients treated with lenalidomide is low. Most patients with VTE had at least one additional risk factor. Recognition of additional risk factors for VTE, with consideration of thrombosis prophylaxis where clinically warranted, is important to improve clinical outcomes in MDS patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Corporation Celgene Corporation Celgene Corporation Celgene Corporation Celgene Corporation
Role of Endogenous Murine Leukemia Virus in Immunologically Triggered Lymphoreticular Tumors. I. Development and Use of Oncogenic Cellfree Preparations Serially Passaged In Vivo2
Authors: Martine Y. K. Armstrong, Nancy H. Ruddle, Muriel B. Lipman, Susan K. Pierce, Frank F. Richards
Journal: JNCI Journal of the National Cancer Institute (1977)

Cellfree extracts (CFEs) prepared from (BALB/cJ × A/J)F1 (CAF1) and (BALB/cJ × C57BL/6J)F1 (CB6F1) mice in which a graft-versus-host reaction (GVHR) has been induced are known 10 be oncogenic, but only after a protracted latent period (mean, 16 mol, Serial passage of such CFEs in successive generations of syngeneic mice inoculated at birth led to the development of two separate oncogenic preparations, the CA series in CAF1 mice and the CB series in CB6F1 mice, in which the mean latent period was reduced to 6 and 12 months, respectively. Both oncogenic preparations contained infectious B-tropic murine leukemia virus (MuLV) and particles with the ultrastructural characteristics of MuLV. No other kind of virus particle was seen. When these preparations were injected into infant syngeneic mice, B-tropic MuLV could be detected in the reticular tissues as early as 2 weeks thereafter. The virus persisted in the reticular tissues and was present in the Iymphoreticular tumors that subsequently developed, However, if the same preparation was injected into young adult recipients, there may have been transient MuLV replication, but the virus subsequently disappeared from the reticular tissues and no Iymphoreticular tumors developed, Previous experiments showed that MuLV was present in CFEs prepared from CAF1 animals with the GVHR but absent in those of normal control mice. Since the Iymphoreticular tumors arising in mice with the GVHR were the same as those induced by the CA and CB MuLV preparations, it was concluded that tumorigenesis in mice with the GVHR was caused by endogenous B-tropic MuLV activated by the immunologic disturbance.
Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice
Authors: Stefan Prokop, Kelly R. Miller, Natalia Drost, Susann Handrick, Vidhu Mathur, Jian Luo, Anja Wegner, Tony Wyss-Coray, Frank L. Heppner
Journal: The Journal of Experimental Medicine (2015)

Although central nervous system–resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), a major pathological hallmark of Alzheimer’s disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ-clearing capabilities. Here, we demonstrate that the conditional ablation of resident microglia in CD11b-HSVTK (TK) mice is followed by a rapid repopulation of the brain by peripherally derived myeloid cells. We used this system to directly assess the ability of peripheral macrophages to reduce Aβ plaque pathology and therefore depleted and replaced the pool of resident microglia with peripherally derived myeloid cells in Aβ-carrying APPPS1 mice crossed to TK mice (APPPS1;TK). Despite a nearly complete exchange of resident microglia with peripheral myeloid cells, there was no significant change in Aβ burden or APP processing in APPPS1;TK mice. Importantly, however, newly recruited peripheral myeloid cells failed to cluster around Aβ deposits. Even additional anti-Aβ antibody treatment aimed at engaging myeloid cells with amyloid plaques neither directed peripherally derived myeloid cells to amyloid plaques nor altered Aβ burden. These data demonstrate that mere recruitment of peripheral myeloid cells to the brain is insufficient in substantially clearing Aβ burden and suggest that specific additional triggers appear to be required to exploit the full potential of myeloid cell–based therapies for AD.
Anaerobic Glycolysis in Spontaneous and Transplanted Liver Tumors of Mice
Authors: Mark W. Woods, George Vlahakis
Journal: JNCI Journal of the National Cancer Institute (1973)

Preoxygenation in vitro of liver slices or spontaneous hepatomas from mouse strains C3H, C3HfB, and C3H-AvyfB, suspended in Krebs-Ringer bicarbonate-glucose-pyruvate at 37° C, markedly increased the (manometric) anaerobic glycolysis in both types of tissue. Relative to liver, hepatoma glycolysis had a higher QCO2N2 increased affinity for glucose, and decreased sensitivity to inhibition by Δ1-testololactone (Δ1-TL). Glycolysis had a considerable rate of decay in liver and hepatoma, particularly with low glucose. While the viable yellow gene (Aτy) of strain C3H-AvyfB increased the occurrence of spontaneous hepatomas, it had little if any effect on glycolysis in either hepatoma or liver. Glycolytic profiles (rate-time curves at different levels of glucose) of primary hepatomas, despite distinct quantitative differences, unmistakably resembled those of liver. In transplanted hepatomas derived from spontaneous primary hepatomas, these hepatic characteristics were maintained. Transplanted cholangioma, apparently derived from a spontaneous bile-duct tumor, had a glycolytic profile distinct from that of hepatomas (higher affinity for glucose, lower rate of glycolytic decay). With respect to QCO2N2 glucose affinity and sensitivity to anti-insulin-type inhibition (Δ1-TL), spontaneous hepatoma development apparently involved the partial reversal of normal glucolytic ontogeny. The data support the view that an increased glucolytic capacity always accompanies hepatoma origin and development. Previous studies have supported the concept that an increased glucolytic capacity always accompanies malignant transformation.
American Association of Cancer Research Showcases Immunotherapy Advances:
Authors: Vicki Brower
Journal: JNCI Journal of the National Cancer Institute (2015)

Patients with advanced, untreated melanoma that took a combination of two immunotherapies, nivolumab and ipilimumab, showed greater improvement than those who took ipilimumab alone, according to a new study.Results from this phase II double-blinded study in 142 patients are especially promising for patients without BRAF mutations, who had an overall response rate of 60%, in contrast to 44% of patients without the mutation.Researchers discussed this and other immunotherapy trials at the meeting of the American Academy of Cancer Research (AACR), in April, and these results were published simultaneously in the New England Journal of Medicine (online April 19, 2015;
Regulator and effector T lymphocytes in late stages of non small cell lung cancer and chronic obstructive pulmonary disease
Authors: Gabriella Galffy, Dora Bartusek, Aron Cseh, Veronika Papp, Eszter Zelenak, Zoltan Sutto, Barna Vasarhelyi, Gyorgy Losonczy
Journal: European Respiratory Journal (2012)

The outcome of lung caner may be determined by anticancer immunresponse. There are only few data available on how DCs (dentritic cell), effector T, NK cells and various regulatory subsets like Treg-s (foxp3+), or NK T-s respond to lung cancer (LC).  Blood was drawn from 50 pts (age 36 to 77) suffering from non-small cell lung cancer in either III/B or IV stages. Since 80% of LC suffered also from chronic obstructive pulmonary disease (COPD), one control group was formed from COPD (n=25) and another one from healthy individuals (n=25). Peripheral blood mononuclear cells were separated and analyzed by FACS using labeled monoclonal antibodies. Activated effector T cells were determined by CD4CD45RO, the naive T cells were specified by CD4CD45RA, the regulatory T lymphocytes by CD4highFoxP3 and dendritic cells by Lin1- HLA DR positivity. The NKT cells were defined by Va24Vb11 (iNKT) and CD161CD3 (NKT) markers.  In lung cancer, the ratio of naiv CD4+ lymphocytes was increased as compared to COPD (p ) . The ratios of iNKT and NKT cells were elevated in LC when compared to COPD (p ) .  The antigen specific immune responses diminished, regarding the decreased level of dentritic cells and increased level of naiv CD4 cells. The elevation of NKT cells represents the propagation of an antigen independent immune response. The rise of regulatory T cells facilitates tumor progression.