tbuckley/cabot-search huggingface dataset:
Improvement in Pulmonary Function and Elastic Recoil after Lung-Reduction Surgery for Diffuse Emphysema
Authors: Frank C. Sciurba, Robert M. Rogers, Robert J. Keenan, William A. Slivka, John Gorcsan, Peter F. Ferson, John M. Holbert, Manuel L. Brown, Rodney J. Landreneau
Journal: New England Journal of Medicine (1996)

Pulmonary function may improve after surgical resection of the most severely affected lung tissue (lung-reduction surgery) in patients with diffuse emphysema. The basic mechanisms responsible for the improvement, however, are not known.We studied 20 patients with diffuse emphysema before and at least three months after either a unilateral or a bilateral lung-reduction procedure. Clinical benefit was assessed by measurement of the six-minute walking distance and the transitional-dyspnea index, which is a subjective rating of the change from base line in functional impairment and the threshold for effort- and task- dependent dyspnea. Pressure-volume relations in the lungs were measured with static expiratory esophageal-balloon techniques, and right ventricular systolic function was assessed by echocardiography.The patients had significant improvement in the transitional-dyspnea index after surgery (P<0.001). The mean (+/-SD) coefficient of retraction, an indicator of elastic recoil of the lung, improved (from 1.3+/-0.6 cm of water per liter before surgery to 1.8+/-0.8 after, P<0.001). Sixteen patients with increased elastic recoil had a greater increase in the distance walked in six minutes than the other four patients, in whom recoil did not increase (P=0.02). The improved lung recoil led to disproportionate decreases in residual volume as compared with total lung capacity (16 percent vs. 6 percent), but the decreases in both values were significant (P<0.001). Forced expiratory volume in one second increased (from 0.87+/-0.36 to 1.11+/-0.45 liters, P<0.001). End-expiratory esophageal pressure also decreased (P=0.002). These improvements in lung mechanics led to a decrease in arterial partial pressure of carbon dioxide form 42+/-6 to 38+/-5 mm Hg (P=0.006). Furthermore, the fractional change in right ventricular area, an indicator of systolic function, increased from 0.33+/-0.11 to 0.38+/-0.010 (P=0.02).Lung-reduction surgery can produce increases in the elastic recoil of the lung in patients with diffuse emphysema, leading to short-term improvement in dyspnea and exercise tolerance.
Which benefit from adding gemcitabine to vinorelbine in elderly (≥70 years) women with metastatic breast cancer? Early interruption of a phase II study
Authors: U. Basso, L. Fratino, A. Brunello, F. Lumachi, G.L. De Salvo, S. Lonardi, C. Ghiotto, H. Koussis, L.M. Pasetto, S. Monfardini
Journal: Annals of Oncology (2006)
Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity.
Authors: Stuart D Dowall, David A Matthews, Isabel García-Dorival, Irene Taylor, John Kenny, Christiane Hertz-Fowler, Neil Hall, Kara Corbin-Lickfett, Cyril Empig, Kyle Schlunegger, John N Barr, Miles W Carroll, Roger Hewson, Julian A Hiscox
Journal: Genome biology (2014)

Ebolaviruses causes a severe and often fatal hemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission.To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naive animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage.Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV.
Inhibition of Phosphodiesterase-4 (PDE4) activity triggers luminal apoptosis and AKT dephosphorylation in a 3-D colonic-crypt model
Authors: Toshiyuki Tsunoda, Takeharu Ota, Takahiro Fujimoto, Keiko Doi, Yoko Tanaka, Yasuhiro Yoshida, Masahiro Ogawa, Hiroshi Matsuzaki, Masato Hamabashiri, Darren R Tyson, Masahide Kuroki, Shingo Miyamoto, Senji Shirasawa
Journal: Molecular Cancer (2012)

Abstract Background We previously established a three-dimensional (3-D) colonic crypt model using HKe3 cells which are human colorectal cancer (CRC) HCT116 cells with a disruption in oncogenic KRAS, and revealed the crucial roles of oncogenic KRAS both in inhibition of apoptosis and in disruption of cell polarity; however, the molecular mechanism of KRAS-induced these 3-D specific biological changes remains to be elucidated. Results Among the genes that were upregulated by oncogenic KRAS in this model, we focused on the phosphodiesterase 4B ( PDE4B ) of which expression levels were found to be higher in clinical tumor samples from CRC patients in comparison to those from healthy control in the public datasets of gene expression analysis. PDE4B2 was specifically overexpressed among other PDE4 isoforms, and re-expression of oncogenic KRAS in HKe3 cells resulted in PDE4B overexpression. Furthermore, the inhibition of PDE4 catalytic activity using rolipram reverted the disorganization of HCT116 cells into the normal physiologic state of the epithelial cell polarity by inducing the apical assembly of ZO-1 (a tight junction marker) and E-cadherin (an adherens junction marker) and by increasing the activity of caspase-3 (an apoptosis marker) in luminal cavities. Notably, rolipram reduced the AKT phosphorylation, which is known to be associated with the disruption of luminal cavity formation and CRC development. Similar results were also obtained using PDE4B2 -shRNAs. In addition, increased expression of PDE4B mRNA was found to be correlated with relapsed CRC in a public datasets of gene expression analysis. Conclusions These results collectively suggested that PDE4B is upregulated by oncogenic KRAS, and also that the inhibition of PDE4 catalytic activity can induce both epithelial cell polarity and luminal apoptosis in CRC, thus highlighting the utility of our 3-D culture (3 DC) model for the KRAS-induced development of CRC in 3-D microenvironment. Indeed, using this model, we found that PDE4B is a promising candidate for a therapeutic target as well as prognostic molecular marker in CRC. Further elucidation of the signaling network of PDE4B2 in 3 DC would provide a better understanding of CRC in vivo .
Precision immunophenotyping by high-throughput TCR sequencing in human glioma
Authors: Jennifer Sims, Boris Grinshpun, Yaping Feng, Timothy Ung, Justin Neira, Jorge Samanamud, Peter Canoll, Yufeng Shen, Peter Sims, Jeffrey Bruce
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immunotherapy for glioblastoma (GBM) is the subject of numerous clinical trials, given the potential for the adaptive immune response to combat this diffusely infiltrating tumor. However, rational application of immunotherapy to these tumors is challenging because of the peculiar
Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis
Authors: Arthur Kaser, Gerald Brandacher, Wolfgang Steurer, Susanne Kaser, Felix A. Offner, Heinz Zoller, Igor Theurl, Walter Widder, Clemens Molnar, Othmar Ludwiczek, Michael B. Atkins, James W. Mier, Herbert Tilg
Journal: Blood (2001)
THE EFFECT OF STAPHYLOCOCCUS AUREUS TOXIN ON THE KIDNEY
Authors: William C. VonGlahn, Julia T. Weld
Journal: The Journal of Experimental Medicine (1935)

1. The hemolytic Staphylococcus aureus elaborates a toxin in vitro that when injected intravenously produces lesions in the kidneys of rabbits and cats. 2. The toxin injures primarily the blood vessels of the kidney.
Proadrenomedullin NH(2)-terminal 20 peptide, a new product of the adrenomedullin gene, inhibits norepinephrine overflow from nerve endings.
Authors: T Shimosawa, Y Ito, K Ando, K Kitamura, K Kangawa, T Fujita
Journal: Journal of Clinical Investigation (1995)

Proadrenomedullin NH(2)-terminal 20 peptide (PAMP) and adrenomedullin, which are derived from proadrenomedullin, exhibit remarkable hypotensive action. We investigated the effect of PAMP and adrenomedullin on peripheral sympathetic neutral transmission. Using perfused rat mesenteric arteries, PAMP (0, 1, 5, and 10 pmol/ml) decreased norepinephrine overflow by periarterial electrical nerve stimulation in a dose-dependent fashion (0.244 +/- 0.043, 0.231 +/- 0.048, 0.195 +/- 0.061 and 0.168 +/- 0.051 ng/gram tissue weigh: NS, P < 0.05, and P < 0.02, respectively). In contrast to PAMP, adrenomedullin (1, 5, and 10 pmol/ml) did not change it. In contrast, vasoconstrictive response of mesenteric arteries to exogenous norepinephrine was significantly attenuated by 10 pmol/ml of adrenomedullin but not by the same dose of PAMP. Calcitonin gene-related peptide (8-37) [CGRP(8-37)], a CGRP receptor antagonist, inhibited the vasodilatory effect of adrenomedullin but could not suppress the sympathoinhibitory effect of PAMP. Neither a nicotinic antagonist, hexamethonium, nor a presynaptic alfa2 antagonist, yohimbine, blocked the sympathoinhibitory effect of PAMP. Thus, it suggests that PAMP and adrenomedullin, which are derived from the same gene, exhibit different hypotensive mechanisms: PAMP inhibits neural transmission at peripheral sympathetic nerve ending, although adrenomedullin directly dilates vascular smooth muscle, possibly through CGRP-like receptor.
Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients.
Authors: I Tardieux, M H Nathanson, N W Andrews
Journal: The Journal of Experimental Medicine (1994)

Trypanosoma cruzi enters cells by a unique mechanism, distinct from phagocytosis. Invasion is facilitated by disruption of host cell actin microfilaments, and involves recruitment and fusion of host lysosomes at the site of parasite entry. These findings implied the existence of transmembrane signaling mechanisms triggered by the parasites in the host cells before invasion. Here we show that infective trypomastigotes or their isolated membranes, but not the noninfective epimastigotes, induce repetitive cytosolic-free Ca2+ transients in individual normal rat kidney fibroblasts, in a pertussis toxin-sensitive manner. Parasite entry is inhibited by buffering or depleting host cell cytosolic-free Ca2+, or by pretreatment with Ca2+ channel blockers or pertussis toxin. In contrast, invasion is enhanced by brief exposure of the host cells to cytochalasin D. These results indicate that a trypomastigote membrane factor triggers cytosolic-free Ca2+ transients in host cells through a G-protein-coupled pathway. This signaling event may promote invasion through modulation of the host cell actin cytoskeleton.
Immunoreactivity for interleukin 3 and 5 and granulocyte/macrophage colony-stimulating factor of intestinal mucosa in bronchial asthma.
Authors: B Wallaert, P Desreumaux, M C Copin, I Tillie, A Benard, J F Colombel, B Gosselin, A B Tonnel, A Janin
Journal: The Journal of Experimental Medicine (1995)

T lymphocytes and eosinophils are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate pathological abnormalities and immunoreactivity for interleukin (IL) 3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) of intestinal mucosa in bronchial asthma. 15 asthmatic patients, 8 nonasthmatic patients with chronic obstructive pulmonary disease, 6 atopic nonasthmatic healthy controls, and 6 nonatopic healthy controls were studied. Duodenal biopsies were performed by endoscopy. A significantly increased number of intraepithelial lymphocytes and eosinophils and a significant accumulation of mononuclear cells (lymphocytes and mast cells) and eosinophils in the lamina propria were detected in asthmatics and atopic controls. Immunostaining with antibodies directed against IL-3, IL-5, and GM-CSF was positive in asthmatics and atopic controls, whereas no staining was observed in nonatopic controls and chronic obstructive pulmonary disease. Combined ultrastructural study and immunogold labeling demonstrated that IL-3, IL-5, and GM-CSF were localized in eosinophils and mast cells. Although devoid of gastrointestinal symptoms, asthmatics and asymptomatic atopics had duodenal pathological abnormalities mimicking those observed in the bronchial mucosa in asthma, suggesting that the whole mucosal immune system is involved in bronchial asthma.
Oxygen in acute and chronic wound healing
Authors: S. Schreml, R.M. Szeimies, L. Prantl, S. Karrer, M. Landthaler, P. Babilas
Journal: British Journal of Dermatology (2010)

Journal Article Oxygen in acute and chronic wound healing Get access S. Schreml, S. Schreml Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar R.M. Szeimies, R.M. Szeimies Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar L. Prantl, L. Prantl Plastic Surgery, University Hospital Regensburg, 93042 Regensburg, Germany Search for other works by this author on: Oxford Academic Google Scholar S. Karrer, S. Karrer Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar M. Landthaler, M. Landthaler Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar P. Babilas P. Babilas Departments of Dermatology Philipp Babilas. E‐mail: philipp.babilas@klinik.uni‐regensburg.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 2, 1 August 2010, Pages 257–268, https://doi.org/10.1111/j.1365-2133.2010.09804.x Published: 01 August 2010
Fluvastatin and Perioperative Events in Patients Undergoing Vascular Surgery
Authors: Olaf Schouten, Eric Boersma, Sanne E. Hoeks, Robbert Benner, Hero van Urk, Marc R.H.M. van Sambeek, Hence J.M. Verhagen, Nisar A. Khan, Martin Dunkelgrun, Jeroen J. Bax, Don Poldermans
Journal: New England Journal of Medicine (2009)

Adverse cardiac events are common after vascular surgery. We hypothesized that perioperative statin therapy would improve postoperative outcomes.In this double-blind, placebo-controlled trial, we randomly assigned patients who had not previously been treated with a statin to receive, in addition to a beta-blocker, either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery. Lipid, interleukin-6, and C-reactive protein levels were measured at the time of randomization and before surgery. The primary end point was the occurrence of myocardial ischemia, defined as transient electrocardiographic abnormalities, release of troponin T, or both, within 30 days after surgery. The secondary end point was the composite of death from cardiovascular causes and myocardial infarction.A total of 250 patients were assigned to fluvastatin, and 247 to placebo, a median of 37 days before vascular surgery. Levels of total cholesterol, low-density lipoprotein cholesterol, interleukin-6, and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group. Postoperative myocardial ischemia occurred in 27 patients (10.8%) in the fluvastatin group and in 47 (19.0%) in the placebo group (hazard ratio, 0.55; 95% confidence interval [CI], 0.34 to 0.88; P=0.01). Death from cardiovascular causes or myocardial infarction occurred in 12 patients (4.8%) in the fluvastatin group and 25 patients (10.1%) in the placebo group (hazard ratio, 0.47; 95% CI, 0.24 to 0.94; P=0.03). Fluvastatin therapy was not associated with a significant increase in the rate of adverse events.In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome. (Current Controlled Trials number, ISRCTN83738615.)
Recognition of unusual presentation of natural killer cell leukemia
Authors: C. M. Gardiner, D. J. Reen, A. O'Meara
Journal: American Journal of Hematology (1995)

Abstract Expansion of the natural killer (NK) subset of lymphocytes represents a rare leukemia phenotype with variations in clinical presentation, morphology, surface phenotype, and effector function. This paper reports on a 5‐year‐old male patient who had an unusual presentation of an NK cell leukemia that was initially diagnosed as neuroblastoma. A bone marrow (BM) aspirate showed clumps of undifferentiated cells with the following phenotype: CD56 bright +, CD33 dim +, CD45‐, CD2‐, CD19‐, CD16‐, and CD57‐. Cytochemistry was noncontributory. The patient, having failed to respond to conventional neuroblastoma chemotherapy, was subsequently diagnosed as having NK cell leukemia based on functional in vitro assays. The patient responded to acute lymphoblastic leukemia (ALL) chemotherapy but relapsed 4 weeks into treatment and eventually died 25 weeks after initial presentation. The cell surface phenotype observed is consistent with a rare NK cell subset, the biology of which has not been well defined. Freshly isolated BM cells killed K562 cells in a conventional 51 Cr‐release assay. Both interleukin‐2 (IL‐2) and interferon‐α (IFN‐α) induced LAK activity against the Daudi cell line. IL‐2 induced proliferation of the leukemic cells. TNF‐α, IFN‐γ, IL‐6, IL‐1ra, and TGF‐β levels were assessed and found to be concentrated in BM, in contrast to plasma samples. TNF‐α was present at a high concentration in BM (150.9 pg/ml), probably a reflection of the associated disease pathology of severe bone pain and pyrexia. In summary, this paper details clinical and laboratory investigations of a leukemia of a rare NK cell subset.
A patient with new onset of thoracic pain, dyspnoea and weight loss
Authors: G. Lohr, C. Luft, K. Lenz
Journal: Gut (2009)

A 55-year-old man with a long history of recurrent alcohol-induced chronic pancreatitis was admitted to our hospital with new onset dyspnoea, epigastric and thoracic pain, and nausea. Clinical examination was in addition to pressure pain and resistance in the epigastrium normal. Laboratory results showed an elevation of inflammation markers (C-reactive protein, 9 mg/dl) and elevated liver (γ-glutamyl transferase, 324 U/l; alkaline phosphatase, 308 U/l) and pancreatic enzymes (amylase, 181 U/l; lipase, 93 U/l).

A computed tomography scan of the abdomen and thorax was performed (figs 1–3).



Figure 1 
Sagittal reconstruction of the abdominal and thoracic computed tomography scan.





Figure 2 
Axial reconstruction of the abdominal and thoracic computed tomography scan.





Figure 3 
Coronal reconstruction of the abdominal and thoracic computed tomography scan. …
Tamoxifen and Breast Cancer Incidence Among Women With Inherited Mutations in BRCA1 and BRCA2
Authors: Mary-Claire King
Journal: JAMA (2001)

ContextAmong cancer-free women aged 35 years or older, tamoxifen reduced the incidence of estrogen receptor (ER)–positive but not ER-negative breast cancer. The effect of tamoxifen on breast cancer incidence among women at extremely high risk due to inheritedBRCA1 or BRCA2mutations is unknown.ObjectiveTo evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations.Design, Setting, and ParticipantsGenomic analysis of BRCA1 and BRCA2 for 288 women who developed breast cancer after entry into the randomized, double-blind Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project (between April 1, 1992, and September 30, 1999).Main Outcome MeasureAmong women with BRCA1 or BRCA2 mutations, incidence of breast cancer among those who were receiving tamoxifen vs incidence of breast cancer among those receiving placebo.ResultsOf the 288 breast cancer cases, 19 (6.6%) inherited disease-predisposing BRCA1 or BRCA2 mutations. Of 8 patients with BRCA1 mutations, 5 received tamoxifen and 3 received placebo (risk ratio, 1.67; 95% confidence interval, 0.32-10.70). Of 11 patients with BRCA2 mutations, 3 received tamoxifen and 8 received placebo (risk ratio, 0.38; 95% confidence interval, 0.06-1.56). From 10 studies, including this one, 83% of BRCA1 breast tumors were ER-negative, whereas 76% of BRCA2 breast tumors were ER-positive.ConclusionTamoxifen reduced breast cancer incidence among healthy BRCA2 carriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast cancer incidence among healthy women with inherited BRCA1 mutations. Whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women with BRCA1 mutations remains unknown.
A Phase I/II Trial of Intratumoral Endoscopic Ultrasound Injection of ONYX-015 with Intravenous Gemcitabine in Unresectable Pancreatic Carcinoma
Authors: J Randolph Hecht, Rudolph Bedford, James L Abbruzzese, Sandeep Lahoti, Tony R Reid, Roy M Soetikno, David H Kirn, Scott M Freeman
Journal: Clinical Cancer Research (2003)

Purpose: Localized pancreatic carcinoma is rarely resectable and is resistant to conventional therapies. ONYX-015 (dl1520) is an E1B-55kD gene-deleted replication-selective adenovirus that preferentially replicates in and kills malignant cells. Endoscopic ultrasound (EUS) has the potential to conveniently and accurately deliver local therapy to the pancreas. Therefore, we undertook a trial of the feasibility, tolerability, and efficacy of EUS injection of ONYX-015 into unresectable pancreatic carcinomas.  Experimental Design: Twenty-one patients with locally advanced adenocarcinoma of the pancreas or with metastatic disease, but minimal or absent liver metastases, underwent eight sessions of ONYX-015 delivered by EUS injection into the primary pancreatic tumor over 8 weeks. The final four treatments were given in combination with gemcitabine (i.v., 1000 mg/m2). Patients received 2 × 1010 (n = 3) or 2 × 1011 (n = 18) virus particles/treatment.  Results: After combination therapy, 2 patients had partial regressions of the injected tumor, 2 had minor responses, 6 had stable disease, and 11 had progressive disease or had to go off study because of treatment toxicity. No clinical pancreatitis occurred despite mild, transient elevations in lipase in a minority of patients. Two patients had sepsis before the institution of prophylactic oral antibiotics. Two patients had duodenal perforations from the rigid endoscope tip. No perforations occurred after the protocol was changed to transgastic injections only.  Conclusions: This study indicates that ONYX-015 injection via EUS into pancreatic carcinomas by the transgastic route with prophylactic antibiotics is feasible and generally well tolerated either alone or in combination with gemcitabine. Transgastric EUS-guided injection is a new and practical method of delivering biological agents to pancreatic tumors.