tbuckley/cabot-search huggingface dataset:
Haemodynamics, exercise capacity and clinical events in pulmonary arterial hypertension
Authors: Gianluigi Savarese, Francesca Musella, Carmen D'Amore, Teresa Losco, Caterina Marciano, Paola Gargiulo, Giuseppe Rengo, Santo Dellegrottaglie, Eduardo Bossone, Dario Leosco, Pasquale Perrone-Filardi
Journal: European Respiratory Journal (2012)

The purpose of this study was to clarify whether changes in cardiopulmonary haemodynamics induced by pharmacological therapy correlate with exercise capacity and clinical events in patients with pulmonary arterial hypertension. 16 randomised trials including 2353 patients, followed up for 16.4±10.6 weeks, measuring cardiopulmonary haemodynamics by right heart catheterisation and reporting clinical events were included. Meta-analysis and meta-regression analysis were performed to assess the effects of treatments on clinical events and the relationship between haemodynamic changes (pulmonary artery pressure, pulmonary vascular resistance, cardiac index and right atrial pressure) and clinical events. Treatments significantly reduced all-cause death (OR 0.5, 95% CI 0.3–0.7; p&lt;0.01), hospitalisation for pulmonary arterial hypertension (OR 0.4, 95% CI 0.2–0.7; p&lt;0.01), initiation of rescue therapy (OR 0.3, 95% CI 0.2–0.6; p&lt;0.01) and the composite outcome (OR 0.3, 95% CI 0.3–0.5; p&lt;0.01). No relationship was found between changes of haemodynamic parameters and clinical events, whereas changes of cardiac index and pulmonary vascular resistance significantly correlated with changes in the 6-min walking distance (r = 0.64, p = 0.03; r = -0.55, p = 0.04, respectively). In patients with pulmonary arterial hypertension, improvements of cardiopulmonary haemodynamics observed in randomised clinical trials correlate with exercise capacity changes but do not predict clinical events in a short-term follow-up.
Neuropeptide Y prevents the blood pressure fall induced by endotoxin in conscious rats with adrenal medullectomy.
Authors: D Evéquoz, B Waeber, J F Aubert, J P Flückiger, J Nussberger, H R Brunner
Journal: Circulation Research (1988)

Neuropeptide Y (NPY) is a vasoconstrictor peptide known to be present in the adrenal medulla, the terminal nerve endings, and in plasma. This study was designed to test whether NPY could prevent the acute blood pressure fall induced by endotoxin administration. Normotensive rats were subjected to adrenal demedullation on the right side and were either adrenalectomized or sham-operated on the left side. Eight to ten days later, NPY (0.07 microgram/min i.v.) or its vehicle were infused for 95 minutes into these conscious, semirestrained rats. The same experiments were performed with rats that received an infusion of epinephrine (0.1 microgram/min). These doses of NPY and epinephrine when given alone had no blood pressure effect. During the last 75 minutes of the 95-minute infusion, endotoxin (lipopolysaccharide Escherichia coli 0.111:B4, 10 micrograms/min i.v.) or its vehicle were administered. In rats with an intact adrenal gland, endotoxin failed to induce hypotension. In rats lacking a functioning adrenal medulla, however, endotoxin induced a pronounced mean blood pressure fall of 55 +/- 11.6 mm Hg (mean +/- SEM). This blood pressure drop could be prevented equally well with NPY and with epinephrine infusion and averaged 11 +/- 2.3 and 16 +/- 2.4 mm Hg, respectively, at the end of the experiment. Additional rats were biadrenalectomized and supplemented with an excess of glucocorticoids and mineralocorticoids. In these rats also, NPY markedly attenuated the blood pressure fall resulting from endotoxemia. These data taken together indicate that in conscious rats with no adrenal medulla, the acute blood pressure fall induced by endotoxin administration is greatly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases.
Authors: E S Dye, R J North
Journal: The Journal of Experimental Medicine (1981)

Progressive growth of the P815 mastocytoma in semisyngeneic mice evokes the generation of a T cell-mediated mechanism of immunosuppression that inhibits the capacity of passively transferred, tumor-sensitized T cells from regressing this tumor in recipient mice. This conclusion is based on two findings: (a) that it is possible to demonstrate adoptive T cell-mediated regression of established tumors, but only if the tumors are growing in T cell-deficient recipients, and (b) that adoptive T cell-mediated regression of tumors in these recipients can be inhibited by the infusion of splenic T cells from T cell-intact, tumor-bearing donors. The results of additional experiments designed to measure the effect of decreasing the number of suppressor cells and the time that they are infused, relative immune cells, indicate that the function of suppressor cells in this model is to inhibit the replication of passively transferred immune T cells. The results obtained with the P815 mastocytoma are similar to those obtained previously with a chemically induced fibrosarcoma. They show, in addition, that passively transferred immune cells are capable of destroying already seeded metastases in T cell-deficient recipients.
Do human myeloma cells directly produce basic FGF?
Authors: Simona Colla, Francesca Morandi, Mirca Lazzaretti, Paola Polistena, Mirija Svaldi, Paolo Coser, Sabrina Bonomini, Magda Hojden, Eugenia Martella, Teodoro Chisesi, Vittorio Rizzoli, Nicola Giuliani
Journal: Blood (2003)
Consensus on the role of human cytomegalovirus in glioblastoma
Authors: Kristine Dziurzynski, Susan M. Chang, Amy B. Heimberger, Robert F. Kalejta, Stuart R Mc Gregor Dallas, Martine Smit, Liliana Soroceanu, Charles S. Cobbs
Journal: Neuro-Oncology (2012)

The human cytomegalovirus (HCMV) and glioma symposium was convened on April 17, 2011 in Washington, DC, and was attended by oncologists and virologists involved in studying the relationship between HCMV and gliomas. The purpose of the meeting was to reach a consensus on the role of HCMV in the pathology of gliomas and to clarify directions for future research. First, the group summarized data that describe how HCMV biology overlaps with the key pathways of cancer. Then, on the basis of published data and ongoing research, a consensus was reached that there is sufficient evidence to conclude that HCMV sequences and viral gene expression exist in most, if not all, malignant gliomas, that HCMV could modulate the malignant phenotype in glioblastomas by interacting with key signaling pathways; and that HCMV could serve as a novel target for a variety of therapeutic strategies. In summary, existing evidence supports an oncomodulatory role for HCMV in malignant gliomas, but future studies need to focus on determining the role of HCMV as a glioma-initiating event.
Insulin Pump Therapy: a Meta-Analysis
Authors: J. Hans DeVries, Robert J. Heine
Journal: Diabetes Care (2003)

Weissberg-Benchell et al. (1) conclude, based on their meta-analysis on the efficacy of continuous subcutaneous insulin infusion (CSII) versus multiple daily injection (MDI) or conventional therapy (CT), that glycohemoglobin is significantly lower with CSII than with injection therapy. It is stated that “the weighted summary mean difference comparing the effect of CSII …
Cell surface expression of class II histocompatibility antigens occurs in the absence of the invariant chain.
Authors: R P Sekaly, C Tonnelle, M Strubin, B Mach, E O Long
Journal: The Journal of Experimental Medicine (1986)

The invariant chain is a glycoprotein transiently associated with the alpha and beta subunits of class II antigens of the major histocompatibility complex during their transport to the cell surface. An expression assay with cDNA clones transfected into simian COS cells was used to test whether the invariant chain is required for assembly and transport of human class II antigens. COS cells do not express detectable levels of RNA from the endogenous invariant chain gene. Cell surface expression of the DP, DQ, and DR antigens was observed in COS cells transfected with the respective alpha and beta chain cDNA clones. Analysis of RNA from the transfected cells showed that the human genes were transcribed in COS cells and that the endogenous simian class II and invariant chain genes were not induced. Cotransfections with an invariant chain cDNA clone did not alter the levels of class II antigens at the cell surface. Biosynthetic labeling and immunoprecipitation demonstrated that the invariant chain cDNA was expressed into a protein which associated with DR alpha and beta chains. Efficient expression of DR antigen in absence of invariant chain was also observed at the surface of a human fibroblast line stably transfected with DR alpha and beta cDNA. This study demonstrates that expression of all three human class II antigens can be achieved with cDNAs cloned in expression vectors. Furthermore, cell surface expression of class II major histocompatibility complex antigens can occur in absence of invariant chain. The postulated role of the invariant chain in class II antigen transport to the cell surface must be reevaluated. The invariant chain may rather be involved in functional properties of class II molecules such as antigen presentation.
Type I Interferons Link Viral Infection to Enhanced Epithelial Turnover and Repair
Authors: Lulu Sun, Hiroyuki Miyoshi, Sofia Origanti, Timothy J. Nice, Alexandra C. Barger, Nicholas A. Manieri, Leslie A. Fogel, Anthony R. French, David Piwnica-Worms, Helen Piwnica-Worms, Herbert W. Virgin, Deborah J. Lenschow, Thaddeus S. Stappenbeck
Journal: Cell Host & Microbe (2014)
Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis
Authors: M A Silva, B Hegab, C Hyde, B Guo, J A C Buckels, D F Mirza
Journal: Gut (2008)

Needle biopsy of a suspicious liver lesion could guide management in the setting of equivocal imaging and serology, although it is not recommended generally because there is the possibility of tumour dissemination outside the liver. The incidence of needle track seeding following biopsy of a suspicious liver lesion is ill-defined, however.A systematic review and meta-analysis of observational studies published before March 2007 was performed. Studies that reported on needle tract seeding following biopsy of suspicious liver lesions were identified. Lesions suspected of being hepatocelleular cancer (HCC) were considered. Data on the type of needle biopsy, diagnosis, incidence of needle track seeding duration to seeding, follow-up and impact on outcome were tabulated.Eight studies identified by systematic review on biopsy of HCC were included in a meta-analysis. The pooled estimate of a patient with seeding per 100 patients with HCC was 0.027 (95% confidence interval (CI) 0.018 to 0.040). There was no difference whether a fixed or random effects model was used. Q was 4.802 with 7 degrees of freedom, p = 0.684; thus the observed heterogeneity was compatible with variation by chance alone. The pooled estimate of a patient with seeding per 100 patients per year was 0.009 (95% CI 0.006 to 0.013), p = 0.686.In this systematic review we have shown that the incidence of needle tract tumour seeding following biopsy of a HCC is 2.7% overall, or 0.9% per year.
Control of myocardial oxygen tension by sympathetic coronary vasoconstriction in the dog.
Authors: E O Feigl
Journal: Circulation Research (1975)

The effect of sympathetic alpha-receptor coronary vasoconstriction on myocardial oxygen tension was studied in open- and closed-chest, chloralose-anesthetized dogs. Blood oxygen tension in the coronary sinus and blood flow in the circumflex coronary artery were continuously measured in a three-part experiment. With stimulation of the left stellate ganglion (15 Hz, 3 msec, 4-7 v, 90-second train) under vagotomy control conditions (part 1), heart rate, blood pressure, and coronary blood flow increased, but coronary sinus oxygen tension decreased from 19 mm Hg to 15 mm Hg. In part 2, beta-receptor blockade with propranolol (2.0 mg/kg. iv) in the same dogs blunted the positive inotropic and chronotropic effects of sympathetic stimulation; coronary alpha-receptor vasoconstriction was unmasked, and coronary sinus blood oxygen tension fell from 17 mm Hg to 11 mm Hg. Since increases in oxygen metabolism were blunted, it appeared that the decrease in coronary sinus oxygen tension was caused by alpha-receptor coronary artery vasoconstriction. This hypothesis was tested in part 3 by the addition of alpha-receptor blockade with Dibozane (3.0 mg/kg, iv). Sympathetic stimulation no longer resulted in a change in either coronary vascular resistance or coronary sinus oxygen tension. These results indicate that the fall in oxygen tension during beta-receptor blockade in part 2 was due to alpha-receptor coronary vasoconstriction. Thus, myocardial oxygen tension may be regulated by coronary sympathetic vasomotion as well as by myocardial oxygen metabolism and local vascular control mechanisms.
Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study
Authors: H. von der Maase, S.W. Hansen, J.T. Roberts, L. Dogliotti, T. Oliver, M.J. Moore, I. Bodrogi, P. Albers, A. Knuth, C.M. Lippert, P. Kerbrat, P. Sanchez Rovira, P. Wersall, S.P. Cleall, D.F. Roychowdhury, I. Tomlin, C.M. Visseren-Grul, P.F. Conte
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m 2 days 1, 8, and 15; cisplatin 70 mg/m 2 day 2) or standard MVAC every 28 days for a maximum of six cycles. RESULTS: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI, 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively) and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue. CONCLUSION: GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.
Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene.
Authors: A A Escalante, E Barrio, F J Ayala
Journal: Molecular Biology and Evolution (1995)

We have analyzed the conserved regions of the gene coding for the circumsporozoite protein (CSP) in 12 species of Plasmodium, the malaria parasite. The closest evolutionary relative of P. falciparum, the agent of malignant human malaria, is P. reichenowi, a chimpanzee parasite. This is consistent with the hypothesis that P. falciparum is an ancient human parasite, associated with humans since the divergence of the hominids from their closest hominoid relatives. Three other human Plasmodium species are each genetically indistinguishable from species parasitic to nonhuman primates; that is, for the DNA sequences included in our analysis, the differences between species are not greater than the differences between strains of the human species. The human P. malariae is indistinguishable from P. brasilianum, and P. vivax is indistinguishable from P. simium; P. brasilianum and P. simium are parasitic to New World monkeys. The human P. vivax-like is indistinguishable from P. simiovale, a parasite of Old World macaques. We conjecture that P. malariae, P. vivax, and P. vivax-like are evolutionarily recent human parasites, the first two at least acquired only within the last several thousand years, and perhaps within the last few hundred years, after the expansion of human populations in South America following the European colonizations. We estimate the rate of evolution of the conserved regions of the CSP gene as 2.46 x 10(-9) per site per year. The divergence between the P. falciparum and P. reichenowi lineages is accordingly dated 8.9 Myr ago. The divergence between the three lineages leading to the human parasites is very ancient, about 100 Myr old between P. malariae and P. vivax (and P. vivax-like) and about 165 Myr old between P. falciparum and the other two.
Efficacy of Administering an Endothelin-receptor Antagonist (SB209670) in Ameliorating Ischemia–Reperfusion Injury in Lung Allografts
Authors: HANI SHENNIB, ALLAN G. L. LEE, JIN Q. KUANG, MASASHI YANAGISAWA, ELIOT H. OHLSTEIN, ADEL GIAID
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The purpose of this study was to determine whether treatment with an endothelin-1 (ET-1)-receptor antagonist could prevent ET-1-mediated ischemia-reperfusion injury and early allograft dysfunction. Eleven dogs were subjected to left lung allotransplantation. Donor lungs were preserved with modified Eurocollins solution and stored at 4 degrees C for 18 to 20 h. Animals received an intravenous infusion of either the ET-receptor antagonist SB209670 (n = 6) (15 microg/kg/min) or saline (control, n = 5), in a blinded fashion. The infusion started 30 min before transplantation and continued for up to 6 h after transplantation. Hemodynamic measurements, blood gas tensions, and plasma samples were obtained with animals functioning solely on the transplanted lung. Open-lung biopsies were obtained for wet-to-dry-weight ratios and histologic and immunohistochemical analyses. Survival at 6 h after transplantation was 40% in the control group and 100% in the treatment group. Pulmonary vascular resistance and lung tissue wet-to-dry-weight ratio were significantly lower in treated animals at 3 and 6 h after transplantation. Histology of the transplanted lungs revealed more intense airway and interstitial inflammatory infiltration and edema in the control group. Arterial and venous plasma ET-1 concentrations increased after transplantation; however, they were significantly higher in the treatment group. Immunohistochemical analysis revealed more intense ET-1 immunostaining in the airways and parenchyma of the treatment group. We conclude that treatment of lung allografts with the mixed endothelin A/endothelin B (ETA/ETB) receptor antagonist SB209670 can ameliorate ischemia-reperfusion injury, resulting in improved graft function and survival after lung transplantation.
Serum -Tocopherol and Subsequent Risk of Lung Cancer Among Male Smokers
Authors: K. Woodson, J. A. Tangrea, M. J. Barrett, J. Virtamo, P. R. Taylor, D. Albanes
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Higher blood levels of α-tocopherol, the predominant form of vitamin E, have been associated in some studies with a reduced risk of lung cancer, but other studies have yielded conflicting results. To clarify this association, we examined the relationship between prospectively collected serum α-tocopherol and lung cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. METHODS: The ATBC Study was a randomized, clinical trial of 29 133 white male smokers from Finland who were 50-69 years old and who had received α-tocopherol (50 mg), β-carotene (20 mg), both, or neither daily for 5-8 years. Data regarding medical histories, smoking, and dietary factors were obtained at study entry, as was a serum specimen for baseline α-tocopherol determination. α -Tocopherol measurements were available for 29 102 of the men, among whom 1144 incident cases of lung cancer were diagnosed during a median observation period of 7.7 years. The association between α-tocopherol and lung cancer was evaluated with the use of multivariate proportional hazards regression. RESULTS: A 19% reduction in lung cancer incidence was observed in the highest versus lowest quintile of serum α-tocopherol (relative risk = 0.81; 95% confidence interval = 0.67-0.97). There was a stronger inverse association among younger men (<60 years), among men with less cumulative tobacco exposure (<40 years of smoking), and possibly among men receiving α-tocopherol supplementation. CONCLUSIONS: In the ATBC Study cohort, higher serum α-tocopherol status is associated with lower lung cancer risk; this relationship appears stronger among younger persons and among those with less cumulative smoke exposure. These findings suggest that high levels of α-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development.
Immunoniodulating properties of lymphocytes activated by farmer's lung associated bacterium <i>Thermoactinomyces vulgaris in vitro</i>
Authors: H. J. W. Jägerroos
Journal: Allergy (1988)

Thermoactinomyces vulgaris , one of the aetiological agents of farmer's lung, was analysed for its ability to activate non‐immune spleen lymphocytes from 10‐ to 14‐ week‐old mice. The lymphocytes were found to exert both enhancing and suppressing signals after activation, depending on the secondary stimulation used. The enhancing effect is due to interleukin‐2 secreted mainly by L3T4+ lymphocytes. The suppressive action is associated with Lyt2+ lymphocytes, which are probably activated by prostaglandins or histamine; but the suppression inducer action of L3T4+ lymphocytes may also be important. Genetic regulation, independent of H‐2K and D, was also detected between different inbred strains of mice in response to T. vulgaris. The genetic regulation appeared associated with the different responsiveness of Lyt‐2 positive lymphocytes between different strains. These results emphasize the importance of nonspecific activation in hypersensitivity disorders induced by microbiol antigens.
Identification of basophils by a mAb directed against pro–major basic protein 1
Authors: Douglas A. Plager, Ellen A. Weiss, Gail M. Kephart, Robert M. Mocharla, Ryoji Matsumoto, James L. Checkel, Lawrence B. Schwartz, Gerald J. Gleich, Kristin M. Leiferman
Journal: Journal of Allergy and Clinical Immunology (2006)