tbuckley/cabot-search huggingface dataset:
THE INTRACELLULAR DISTRIBUTION OF LANSING POLIOMYELITIS VIRUS IN THE CENTRAL NERVOUS SYSTEM OF INFECTED COTTON RATS
Authors: Carlton E. Schwerdt, Arthur B. Pardee
Journal: The Journal of Experimental Medicine (1952)

A procedure has been described for the centrifugal fractionation of the cellular particulate components of CNS tissue infected with poliomyelitis virus. A study of the distribution of infectivity among these components revealed that approximately four-fifths of the virus is found free in the submicroscopic particle fraction. The validity of the conclusion that the virus is located in this fraction of the intact neuron is discussed.
Ultrasonographic findings in Crohn's disease Reply
Authors: V ARIENTI
Journal: Gut (2000)

Editor,—We read with interest the paper by Gasche et al ( Gut 1999; 44 :112–117) on the accuracy of transabdominal ultrasound in the detection of complications in Crohn's disease. The authors evaluated 33 patients with Crohn's disease who had resective bowel surgery. The results were impressive: 87% sensitivity with 90% specificity in the diagnosis of entero-enteric fistulas; 100% sensitivity with 92% specificity in the diagnosis of intra-abdominal abscesses; and 100% sensitivity with 91% specificity in the diagnosis of strictures. However, these data are in contrast with those reported by Maconi and colleagues1 who found very low sensitivity (50%) with 95.5% specificity in ultrasound detection of entero-enteric fistulas.

The difference in levels of sensitivity in these studies could be explained by the use of different standards and also, in our opinion, by varying definitions of fistulas. Gasche and colleagues considered fistulas to be …
Store–Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein Expression
Authors: Peiwen Wu, Yanxia Wang, Mark E. Davis, Jonathan E. Zuckerman, Sarika Chaudhari, Malcolm Begg, Rong Ma
Journal: Journal of the American Society of Nephrology (2015)

Accumulation of extracellular matrix derived from glomerular mesangial cells is an early feature of diabetic nephropathy. Ca(2+) signals mediated by store-operated Ca(2+) channels regulate protein production in a variety of cell types. The aim of this study was to determine the effect of store-operated Ca(2+) channels in mesangial cells on extracellular matrix protein expression. In cultured human mesangial cells, activation of store-operated Ca(2+) channels by thapsigargin significantly decreased fibronectin protein expression and collagen IV mRNA expression in a dose-dependent manner. Conversely, inhibition of the channels by 2-aminoethyl diphenylborinate significantly increased the expression of fibronectin and collagen IV. Similarly, overexpression of stromal interacting molecule 1 reduced, but knockdown of calcium release-activated calcium channel protein 1 (Orai1) increased fibronectin protein expression. Furthermore, 2-aminoethyl diphenylborinate significantly augmented angiotensin II-induced fibronectin protein expression, whereas thapsigargin abrogated high glucose- and TGF-β1-stimulated matrix protein expression. In vivo knockdown of Orai1 in mesangial cells of mice using a targeted nanoparticle siRNA delivery system resulted in increased expression of glomerular fibronectin and collagen IV, and mice showed significant mesangial expansion compared with controls. Similarly, in vivo knockdown of stromal interacting molecule 1 in mesangial cells by recombinant adeno-associated virus-encoded shRNA markedly increased collagen IV protein expression in renal cortex and caused mesangial expansion in rats. These results suggest that store-operated Ca(2+) channels in mesangial cells negatively regulate extracellular matrix protein expression in the kidney, which may serve as an endogenous renoprotective mechanism in diabetes.
Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial
Authors: Jayant S Vaidya, David J Joseph, Jeffrey S Tobias, Max Bulsara, Frederik Wenz, Christobel Saunders, Michael Alvarado, Henrik L Flyger, Samuele Massarut, Wolfgang Eiermann, Mohammed Keshtgar, John Dewar, Uta Kraus-Tiefenbacher, Marc Sütterlin, Laura Esserman, Helle MR Holtveg, Mario Roncadin, Steffi Pigorsch, Marinos Metaxas, Mary Falzon, April Matthews, Tammy Corica, Norman R Williams, Michael Baum
Journal: The Lancet (2010)
Effects of granulocyte-macrophage colony-stimulating factor and dose intensification of V-ICE chemotherapy in small-cell lung cancer: a prospective randomized study of 300 patients.
Authors: W P Steward, J von Pawel, U Gatzemeier, P Woll, N Thatcher, G Koschel, L Clancy, J Verweij, R de Wit, W Pfeifer, J Fennelly, M von Eiff, J Frisch
Journal: Journal of Clinical Oncology (1998)

To assess whether granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the toxicity of chemotherapy and alters delivered dose-intensity. To assess the feasibility of dose-intensification of chemotherapy in small-cell lung cancer (SCLC) and determine whether it has an impact on outcome.Patients with good- or intermediate-prognosis SCLC entered a prospective multicenter study that involved a 2 x 2 factorial design with randomization to six cycles of chemotherapy with ifosfamide 5 g/m2, carboplatin 300 mg/m2, etoposide 120 mg/m2 intravenously (I.V.) on days 1 and 2 and 240 mg/m2 orally on day 3, and vincristine 0.5 mg/m2 I.V. on day 15 (V-ICE) every 3 weeks (intensified arm) or every 4 weeks (standard arm). A second double-blind randomization to subcutaneous GM-CSF (250 microg/m2/d) or placebo for 14 days between chemotherapy cycles was made.Three hundred patients were entered. Myelosuppression was the main toxicity, with no significant difference in the incidence or grade between treatment groups. The incidence of febrile neutropenia and bacteriologically confirmed sepsis was unaffected by chemotherapy schedule or use of GM-CSF. Twenty-six percent greater dose-intensity was delivered in the intensified arm, with a trend for greater dose-intensity for those who received GM-CSF. Eighty-three percent of patients achieved a response (51% complete response [CR] rate), with no significant difference in response rates between treatment groups. Survival was significantly increased in the intensified compared with the standard arm (P = .0014); median survival rates were 443 versus 351 days and 2-year survival rates were 33% versus 18%, respectively.GM-CSF does not reduce the incidence of complications from myelosuppression of aggressive chemotherapy. Dose intensification of V-ICE to a 3-week schedule in SCLC is not associated with increased toxicity, but appears to improve survival significantly. Future studies should aim to deliver chemotherapy in maximal-tolerated dose-intensities.
Lung transplant outcomes: a review of survival, graft function, physiology, health-related quality of life and cost-effectiveness
Authors: S.M. Studer, R.D. Levy, K. McNeil, J.B. Orens
Journal: European Respiratory Journal (2004)

The success of lung transplantation has improved over time as evidenced by better long-term survival and functional outcomes. Despite the success of this procedure, there are numerous problems and complications that may develop over the life of a lung transplant recipient. With proper monitoring and treatment, the frequency and severity of these problems can be decreased. However, significant improvement for the overall outcomes of lung transplantation will only occur when better methods exist to prevent or effectively treat chronic rejection.
Large Nontransplanted Hepatocellular Carcinoma in Woodchucks: Treatment With Adenovirus-Mediated Delivery of Interleukin 12/B7.1 Genes
Authors: B. M. Putzer, T. Stiewe, F. Rodicker, O. Schildgen, S. Ruhm, O. Dirsch, M. Fiedler, U. Damen, B. Tennant, C. Scherer, F. L. Graham, M. Roggendorf
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Cytokine-based gene therapy strategies efficiently stimulate immune responses against many established transplanted tumors, leading to rejection of the tumor. In this study, we investigated the therapeutic potential of cancer immunotherapy in a clinically more relevant model, woodchucks with primary hepatocellular carcinomas induced by woodchuck hepatitis virus. Methods: Large (2–5 cm), established intrahepatic tumors were given an injection once with 1 × 109 plaque-forming units of AdIL-12/B7.1, an adenovirus vector carrying genes for murine interleukin 12 and B7.1, or of AdEGFP, the control virus, and regression of the tumors was then monitored. Five animals were used in total. Results: In four tumor-bearing animals, the antitumor response was assessed by autopsy and histologic analysis within 1–2 weeks after treatment. In all animals treated with AdIL-12/B7.1 therapy versus AdEGFP therapy, we observed substantial tumor regression (P = .006; two-sided unpaired Student's t test) accompanied by a massive infiltration of T lymphocytes. These tumors also contained increased levels of CD4+ and CD8+ T cells and interferon gamma (IFN γ). In continuously growing tumor nodules given an injection of the control virus or in nontumoral liver, no such effects (i.e., tumor regression and increased levels of CD4+ and CD8+ T cells and IFN γ) were detected. In the fifth animal, monitored for long-term antitumor efficacy by magnetic resonance imaging (MRI) after intratumoral vector administration by MRI guidance, the tumor was almost completely eliminated (≥95%) 7 weeks after treatment. Conclusion: Adenovirus vector-based immunotherapy appears to be an effective treatment of large nontransplanted (orthotopic) tumors that acquire malignant characteristics in a stepwise process, reflecting the real-world scenario of hepatocellular carcinoma in humans.
Stromal Cell–Derived Factor-1α Plays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury
Authors: J. Dawn Abbott, Yan Huang, Dingang Liu, Reed Hickey, Diane S. Krause, Frank J. Giordano
Journal: Circulation (2004)

Background— After myocardial infarction (MI), bone marrow–derived cells (BMDCs) are found within the myocardium. The mechanisms determining BMDC recruitment to the heart remain unclear. We investigated the role of stromal cell–derived factor-1α (SDF-1) in this process. Methods and Results— MI produced in mice by coronary ligation induced SDF-1 mRNA and protein expression in the infarct and border zone and decreased serum SDF-1 levels. By quantitative polymerase chain reaction, 48 hours after intravenous infusion of donor-lineage BMDCs, there were 80.5±15.6% more BDMCs in infarcted hearts compared with sham-operated controls ( P &lt;0.01). Administration of AMD3100, which specifically blocks binding of SDF-1 to its endogenous receptor CXCR4, diminished BMDC recruitment after MI by 64.2±5.5% ( P &lt;0.05), strongly suggesting a requirement for SDF-1 in BMDC recruitment to the infarcted heart. Forced expression of SDF-1 in the heart by adenoviral gene delivery 48 hours after MI doubled BMDC recruitment over MI alone ( P &lt;0.001) but did not enhance recruitment in the absence of MI, suggesting that SDF-1 can augment, but is not singularly sufficient for, BDMC recruitment to the heart. Gene expression analysis after MI revealed increased levels of several genes in addition to SDF-1, including those for vascular endothelial growth factor, matrix metalloproteinase-9, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, which might act in concert with SDF-1 to recruit BMDCs to the injured heart. Conclusion— SDF-1/CXCR4 interactions play a crucial role in the recruitment of BMDCs to the heart after MI and can further increase homing in the presence, but not in the absence, of injury.
Can woodpeckers play rugby or Charles Darwin, where are you when we need you?
Authors: P McCrory
Journal: British Journal of Sports Medicine (2006)

There are those unenlightened folks out there who see rugby players as the classic example of coming from the shallow end of the gene pool. This is, of course, contrasted with the sport of cricket, which is seen to represent the pinnacle of human endeavour. So sublime is cricket, that Americans simply cannot understand it.

There is also an argument to be made that cricket represents intelligent design, being hand delivered from God to Moses along with the Ten Commandments, whereas derivative sports, such as baseball, represent evolution. I guess for Moses’ followers who spent forty years wandering in the wilderness, a game that took five days to finish seemed like a good idea at the time.

At a future sports medicine meeting, we should have a debate on this issue, which could be modelled on the famous Oxford evolution debate of 1860 where Thomas Huxley notably replied to Samuel Wilberforce, then Bishop of Oxford, that he “would rather be descended from an ape than from a cultivated man who used his gifts of culture and eloquence in the service of prejudice and falsehood”. The apocryphal story that arose from that quote was that Huxley had said he would rather be an ape than a Bishop. Perhaps the sports medicine equivalent would be that he would rather be an ape than a rugby player. That is, of course, assuming that there is a difference.

But what of …
Cardiac involvement in Whipple's disease.
Authors: H A McAllister, J J Fenoglio
Journal: Circulation (1975)

Although cardiac involvement in Whipple's disease has been reported previously, the extent and significance of such involvement has not been stressed. In our series of 19 patients, 58% had clinical cardiac findings and 79% had gross cardiac lesions at autopsy. Histologically there were PAS-positive macrophages in the pericardium, myocardium, and valves of each of these patients. These collections of macrophages were associated with chronic inflammatory cells and foci of fibrosis with resultant adhesive pericarditis, focal myocardial fibrosis similar to the fibrosis of idiopathic cardiomyopathy, and valvular fibrosis with deformity grossly resembling the valvular lesions of chronic rheumatic heart disease. Four of the patients with mitral valvular deformity had cardiac murmurs, and ECG changes were noted in six patients with mitral myocardial fibrosis. In addition, pericardial friction rubs were heard in two patients. By electron microscopy rod-shaped bodies, presumably bacteria, were noted in the mitral valve and myocardium. The structures are identical to those described in the small intestinal mucosa of patients with Whipple's disease and presumably are the causative agent of the pancardiopathy.
Transfection efficiency and toxicity following delivery of naked plasmid DNA and cationic lipid–DNA complexes to ovine lung segments
Authors: Michael Emerson, Louise Renwick, Stephen Tate, Susan Rhind, Elspeth Milne, Hazel Painter (née Alsop), A.Christopher Boyd, Gerry McLachlan, Uta Griesenbach, Seng H Cheng, Deborah R Gill, Stephen C Hyde, Alison Baker, Eric W Alton, David J Porteous, D.David S Collie
Journal: Molecular Therapy (2003)

We defined, using a novel large animal model system, the acute pathologic response to localized pulmonary administration of either naked plasmid DNA (pDNA) or cationic lipid–pDNA complexes (pDNA:GL67) and related such responses to concomitant indicators of transfection efficiency, namely levels of chloramphenicol acetyl transferase (CAT) protein and mRNA in specific lung tissue compartments. We instilled doses of 0.2, 1, and 5 mg pDNA to spatially distinct lung segments in six anesthetized sheep and doses of 0.2, 1, and 5 mg pDNA:GL67 to a further six sheep. Twenty-four hours after gene delivery the sheep were euthanized and necropsy examination with sampling of relevant tissues was carried out. Levels of plasmid-derived CAT-specific mRNA and CAT protein in samples derived from segments treated with either pDNA or pDNA:GL67 increased in relation to the administered dose. Levels of mRNA and protein expression were greater for pDNA:GL67 than for pDNA alone. A significant correlation was observed between mRNA and protein expression in samples derived from airways treated with pDNA:GL67. Histopathological changes following administration of both pDNA and pDNA:GL67 were characterized by a neutrophilic inflammation predominantly oriented on airways. The severity of the inflammatory response appeared to correlate with the administered dose of DNA and was generally more severe for pDNA:GL67.
Loss of normal cyclical beta 2 adrenoceptor regulation and increased premenstrual responsiveness to adenosine monophosphate in stable female asthmatic patients
Authors: K. S. Tan, L. C. McFarlane, B. J. Lipworth
Journal: Thorax (1997)

BACKGROUND: A study was undertaken to investigate the influence of the menstrual cycle on airway responsiveness and beta 2 adrenoceptor function in female asthmatic patients. It has previously been shown that normal women exhibit cyclical changes in beta 2 adrenoceptor function with an increase in beta 2 adrenoceptor density in the luteal phase during the premenstrual period. METHODS: Fifteen women with stable, well controlled asthma (mean forced expiratory volume in one second (FEV1) 2.971 (93.8% predicted)) were evaluated. Measurements were made at the follicular phase (days 1-6) and the luteal phase (days 21-24) of the menstrual cycle. Airway responsiveness was assessed using adenosine 59-monophosphate (AMP) and expressed as PC20 AMP. Beta 2 adrenoceptor function was evaluated by measuring lymphocyte beta 2 adrenoceptor parameters and constructing dose-response curves to salbutamol (100-1600 micrograms). The levels of female sex hormones were also measured at both phases of the cycle. RESULTS: There were significant increases in serum levels of both oestradiol (2.2-fold, p &lt; 0.001) and progesterone (7.2-fold, p &lt; 0.05) between the follicular and luteal phases. Geometric mean PC20 AMP was 19.0 mg/ml and 7.6 mg/ml during the follicular and luteal phases, respectively (p &lt; 0.05), a 2.51-fold difference (95% CI 1.19 to 5.30) amounting to 1.33 doubling doses of AMP. There was no change in lymphocyte beta 2 adrenoceptor parameters or in airway beta 2 adrenoceptor responses to salbutamol between the two phases. CONCLUSIONS: Despite an appropriate rise in female sex hormones during the luteal period, beta 2 adrenoceptor regulation in female asthmatic subjects shows a loss of the normal cyclical pattern. In addition, there were cyclical changes in airway responsiveness to AMP which was highest during the premenstrual period. Thus, drugs such as theophylline which block adenosine receptors warrant investigation in premenstrual asthma.
Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation
Authors: Alex R Horsley, Jane C Davies, Robert D Gray, Kenneth A Macleod, Jackie Donovan, Zelena A Aziz, Nicholas J Bell, Margaret Rainer, Shahrul Mt-Isa, Nia Voase, Maria H Dewar, Clare Saunders, James S Gibson, Javier Parra-Leiton, Mia D Larsen, Sarah Jeswiet, Samia Soussi, Yusura Bakar, Mark G Meister, Philippa Tyler, Ann Doherty, David M Hansell, Deborah Ashby, Stephen C Hyde, Deborah R Gill, Andrew P Greening, David J Porteous, J Alastair Innes, A Christopher Boyd, Uta Griesenbach, Steve Cunningham, Eric WFW Alton
Journal: Thorax (2013)

<h3>Background</h3> Clinical trials in cystic fibrosis (CF) have been hindered by the paucity of well characterised and clinically relevant outcome measures. <h3>Aim</h3> To evaluate a range of conventional and novel biomarkers of CF lung disease in a multicentre setting as a contributing study in selecting outcome assays for a clinical trial of <i>CFTR</i> gene therapy. <h3>Methods</h3> A multicentre observational study of adult and paediatric patients with CF (&gt;10 years) treated for a physician-defined exacerbation of CF pulmonary symptoms. Measurements were performed at commencement and immediately after a course of intravenous antibiotics. Disease activity was assessed using 46 assays across five key domains: symptoms, lung physiology, structural changes on CT, pulmonary and systemic inflammatory markers. <h3>Results</h3> Statistically significant improvements were seen in forced expiratory volume in 1 s (p&lt;0.001, n=32), lung clearance index (p&lt;0.01, n=32), symptoms (p&lt;0.0001, n=37), CT scores for airway wall thickness (p&lt;0.01, n=31), air trapping (p&lt;0.01, n=30) and large mucus plugs (p=0.0001, n=31), serum C-reactive protein (p&lt;0.0001, n=34), serum interleukin-6 (p&lt;0.0001, n=33) and serum calprotectin (p&lt;0.0001, n=31). <h3>Discussion</h3> We identify the key biomarkers of inflammation, imaging and physiology that alter alongside symptomatic improvement following treatment of an acute CF exacerbation. These data, in parallel with our study of biomarkers in patients with stable CF, provide important guidance in choosing optimal biomarkers for novel therapies. Further, they highlight that such acute therapy predominantly improves large airway parameters and systemic inflammation, but has less effect on airway inflammation.
Strategies for Improving Survival After In-Hospital Cardiac Arrest in the United States: 2013 Consensus Recommendations
Authors: Laurie J. Morrison, Robert W. Neumar, Janice L. Zimmerman, Mark S. Link, L. Kristin Newby, Paul W. McMullan, Terry Vanden Hoek, Colleen C. Halverson, Lynn Doering, Mary Ann Peberdy, Dana P. Edelson
Journal: Circulation (2013)

T he goal of this statement is to develop consensus recom- mendations aimed at measuring and optimizing outcomes after in-hospital cardiac arrest (IHCA).For the purposes of this statement, IHCA is defined as a cardiac arrest that occurs in a hospital (whether the patient is admitted or not) and for which resuscitation is attempted with chest compressions, defibrillation, or both.
Gene Expression Profile Correlates with T-Cell Infiltration and Relative Survival in Glioblastoma Patients Vaccinated with Dendritic Cell Immunotherapy
Authors: Robert M. Prins, Horacio Soto, Vera Konkankit, Sylvia K. Odesa, Ascia Eskin, William H. Yong, Stanley F. Nelson, Linda M. Liau
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To assess the feasibility, safety, and toxicity of autologous tumor lysate–pulsed dendritic cell (DC) vaccination and toll-like receptor (TLR) agonists in patients with newly diagnosed and recurrent glioblastoma. Clinical and immune responses were monitored and correlated with tumor gene expression profiles. Experimental Design: Twenty-three patients with glioblastoma (WHO grade IV) were enrolled in this dose-escalation study and received three biweekly injections of glioma lysate-pulsed DCs followed by booster vaccinations with either imiquimod or poly-ICLC adjuvant every 3 months until tumor progression. Gene expression profiling, immunohistochemistry, FACS, and cytokine bead arrays were performed on patient tumors and peripheral blood mononuclear cells. Results: DC vaccinations are safe and not associated with any dose-limiting toxicity. The median overall survival from the time of initial surgical diagnosis of glioblastoma was 31.4 months, with a 1-, 2-, and 3-year survival rate of 91%, 55%, and 47%, respectively. Patients whose tumors had mesenchymal gene expression signatures exhibited increased survival following DC vaccination compared with historic controls of the same genetic subtype. Tumor samples with a mesenchymal gene expression signature had a higher number of CD3+ and CD8+ tumor-infiltrating lymphocytes compared with glioblastomas of other gene expression signatures (P = 0.006). Conclusion: Autologous tumor lysate–pulsed DC vaccination in conjunction with TLR agonists is safe as adjuvant therapy in newly diagnosed and recurrent glioblastoma patients. Our results suggest that the mesenchymal gene expression profile may identify an immunogenic subgroup of glioblastoma that may be more responsive to immune-based therapies. Clin Cancer Res; 17(6); 1603–15. ©2010 AACR.