tbuckley/cabot-search huggingface dataset:
Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia
Authors: Linda Andersson, Margareta Scharin Täng, Annika Lundqvist, Malin Lindbom, Ismena Mardani, Per Fogelstrand, Puja Shahrouki, Björn Redfors, Elmir Omerovic, Max Levin, Jan Borén, Malin C. Levin
Journal: Cardiovascular Research (2015)

In myocardial ischaemia, vascular endothelial growth factor (VEGF) induces permeability by activating a signalling pathway that includes VEGF receptor 2 (VEGFR2), resulting in increased oedema and inflammation and thereby expanding the area of tissue damage. In this study, we investigated the role of receptor-interacting protein 2 (Rip2) in VEGF signalling and myocardial ischaemia/reperfusion injury. To determine whether Rip2 has a role in VEGF signalling, we used cultured endothelial cells in which Rip2 was or was not inactivated. In Rip2-deficient endothelial cells, stimulation with VEGF resulted in more rapid kinetics of VEGFR2 phosphorylation than in control cells. Rip2 deficiency also enhanced VEGF-induced activation of ERK1/2, suggesting an increased propensity for endothelial permeability. In a mouse model of myocardial ischaemia, Rip2 deficiency resulted in enhanced vascular permeability, increased oedema and expanding area of myocardial damage, and markedly reduced heart function after long-term follow-up. Our results show that Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. These findings indicate that Rip2 may be a promising novel therapeutic target to reduce excess vascular permeability in ischaemic heart disease.
Combination chemotherapy with gemcitabine and ifosfamide as second-line treatment in metastatic urothelial cancer. A phase II trial conducted by the Hellenic Cooperative Oncology Group
Authors: D. Pectasides, G. Aravantinos, H. Kalofonos, C. Kiamouris, D. Bafaloukos, N. Xiros, C. Nicolaides, A. Visvikis, M.A. Dimopoulos
Journal: Annals of Oncology (2001)
Intracellular glutathione redox status in human dendritic cells regulates IL-27 production and T-cell polarization
Authors: Y. Kamide, M. Utsugi, K. Dobashi, A. Ono, T. Ishizuka, T. Hisada, Y. Koga, K. Uno, J. Hamuro, M. Mori
Journal: Allergy (2011)

Glutathione redox status, changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione, plays a significant role in various aspects of cellular function. In this study, we examined whether intracellular glutathione redox status in human dendritic cells (DCs) regulates the polarization of Th1/Th2 balance.Human monocyte-derived DCs (MD-DCs) treated with glutathione reduced form ethyl ester (GSH-OEt) or L-buthionine-(S,R)-sulfoximine (BSO) were stimulated by lipopolysaccharide (LPS), and the levels of polarization cytokines were measured. Next, DCs matured by LPS or thymic stromal lymphopoietin (TSLP) were cocultured with allogeneic CD4(+) naive T cells and Th1/Th2 balance was evaluated by cytokine production from the primed T cells.Monocyte-derived DCs exposed to GSH-OEt and BSO had increased and decreased intracellular GSH contents, respectively. Lipopolysaccharide-induced interleukin (IL)-27 production was enhanced by GSH-OEt and suppressed by BSO, but neither GSH-OEt nor BSO affected the expression of HLA-DR, CD80, CD83, or CD86. Mature GSH-OEt-treated MD-DCs enhanced interferon (IFN)-γ production from CD4(+) T cells compared with nontreated MD-DCs, and small interfering RNA (siRNA) against IL-27 suppressed the effect of GSH-OEt on IFN-γ production. Additionally, although human myeloid DCs activated by TSLP (TSLP-DCs) prime naïve CD4(+) T cells to differentiate into Th2 cells, treatment of TSLP-DCs with GSH-OEt reduced IL-13 production and enhanced IFN-γ production by CD4(+) T cells. Interleukin-27 siRNA attenuated the inhibitory effect of GSH-OEt on Th2 polarization.Our results reveal that Th1 and Th2 responses are controlled by intracellular glutathione redox status in DCs through IL-27 production.
Natriuretic peptide as a prognostic biomarker in septic shock in respiratory intensive care
Authors: Carlos Lopes, Sara Carvalho, Elsa Fragoso, Pilar Azevedo, Jorge Monteiro, Filipe Monteiro, Cristina Bárbara
Journal: European Respiratory Journal (2013)

To investigate whether NT-proBNP can be used as a prognostic factor in septic shock patients admitted to our Respiratory Intensive Care Unit (RICU).  We did a retrospective study over a 4 year period. All patients admitted with or who developed septic shock during their RICU stay were enrolled. Patient’s demographic data, comorbidities, NT-proBNP levels, glomerular filtration rate (GFR), severity index APACHE II scores and mortality rate were compared between survivors and non-survivors. NT-proBNP levels were determined within 48-72h of admission and were classified according to patient’s age and renal function.  During the study period 31 patients with septic shock were identified. Average age 64 ± 16 years old, 26 were males. Mean APACHE II score 29,2 ± 9,3; mean GFR 66,4 ± 58,2 ml/min/1,7 m2. The most frequent primary diagnosis was Pneumonia. Mortality rate was 87,1% (27 patients). Patients were then divided into two groups according to mortality recorded in the unit. The mean NT-proBNP levels was higher in the survivors group (17530,5 ± 27251 vs 14754,93 ± 23133,43 pg/ml). APACHE II was positively correlated with NT-proBNP (R=0,496, p=0,05). NT-proBNP levels didn9t seem to have influenced mortality (p=0,798).  Our results don9t support the use of NT-proBNP levels as a prognostic factor in septic shock patients. However, the positive correlation observed between NT-proBNP levels and APACHE II scores predicts that NT-proBNP can be used at least as a surrogate marker of disease severity.  These results may be due to the small sample size and to the high prevalence of chronic respiratory failure and preexisting cardiac diseases among our patients, which can lead to high basal levels of NT-proBNP.
Steroid-free immunosuppression after renal transplantation.
Authors: D E Hricik, W L Kupin, M R First
Journal: Journal of the American Society of Nephrology (1994)

Concerns about the side effects of chronic steroid therapy have prompted increasing interest in steroid-free immunosuppression for renal transplant recipients who are maintained on cyclosporine-based regimens. Studies to date suggest that at least 50% of cyclosporine-treated patients can be managed without steroid therapy. Reported benefits of avoiding or withdrawing steroid therapy have included improvements in hyperlipidemia, hypertension, and glucose intolerance and accelerated growth in children. Whether these effects will increase patient or allograft survival remains to be proved. Furthermore, the benefits of steroid-free immunosuppression must be weighed against the risk of precipitating allograft rejection. Although the elimination of steroids clearly increases the short-term risk of acute rejection, further studies are needed to determine the effects of steroid-free immunosuppression on long-term allograft function and to identify clinical or immunologic factors that can predict a successful outcome after the elimination of steroids.
Clarithromycin and amikacin vs. clarithromycin and moxifloxacin for the treatment of post-acupuncture cutaneous infections due to Mycobacterium abscessus: a prospective observational study
Authors: W.S. Choi, M.J. Kim, D.W. Park, S.W. Son, Y.K. Yoon, T. Song, S.M. Bae, J.W. Sohn, H.J. Cheong, M.J. Kim
Journal: Clinical Microbiology and Infection (2010)
p53 and c-jun Expression in Urinary Bladder Transitional Cell Carcinoma: Correlation with Proliferating Cell Nuclear Antigen (PCNA) Histological Grade and Clinical Stage
Authors: Antigone Skopelitou, Michael Hadjiyannakis, Demetrios Dimopoulos, Sevasti Kamina, Olga Krikoni, Vana Alexopoulou, Constantinos Rigas, Niki J. Agnantis
Journal: European Urology (1997)
Cervical Cancer in Yugoslavia. I. Antibodies to Genital Herpesvirus in Cases and Controls2
Authors: Irving I. Kessler, Živko Kulčar, William E. Rawls, Stanislav Smerdel, Marija Strnad, Abraham M. Lilienfeld
Journal: JNCI Journal of the National Cancer Institute (1974)

A broadly based epidemiologic investigation of cervical cancer, with special reference to the herpesvirus hypothesis, was recently completed in Yugoslavia. A total of 350 women < 65 years old with histologically confirmed squamous carcinoma of the uterine cervix and an equal number of other currently hospitalized women were interviewed, examined, and bled for measurement of neutralizing antibodies to oral (HSV-l) and genital (HSV-2) herpesviruses. No pattern was discernible in the distribution of HSV-l titers. However, for both Moslems and non-Moslems in each age group studied, as well as in all combined, HSV-2 titers were higher among cases than controls. The ratio of HSV-2 to HSV-l mean log titers was also significantly higher in each group of cases than in the corresponding controls. Furthermore, HSV-2 antibody prevalence- as judged by II /I titer ratios > 84-was significantly greater among cases than among controls, both Moslem and non-Moslem, with a relative risk of approximately 2. It is the consistent direction of these findings, rather than their absolute numerical value, that is regarded as most impressive. The results of this investigation lend further credence to the herpesvirus hypothesis in cervical cancer.
Single-Agent or Doublets As Second-Line Chemotherapy After Folfirinox in Patients with Locally Advanced or Metastatic Pancreatic Cancer
Authors: C. Pellei, A. Bittoni, K. Andrikou, A. Lanese, M. Santoni, A. Conti, F. Aroldi, S. Delcuratolo, M. Russano, V. Vaccaro, N. Silvestris, M. Milella, D. Santini, A. Zaniboni, S. Cascinu
Journal: Annals of Oncology (2014)
Quantitative measurement of JAK2 V617F mutation in myeloproliferative disorders. Validation and qualification of a new RQPCR diagnostic assay.
Authors: Olivier Biglia, Marc Essodaigui, Marie Joelle Mozziconacci, Sylvie Hermouet, Fabienne Hermitte, Nicolas Maroc
Journal: Clinical Cancer Research (2006)

A4  JAK2 V617F is a mutation found in the majority of patients with polycythemia vera (PV), and a significant number of patients with essential thrombocytopemia (ET) and chronic idiopathic myelofibrosis (CIMF).The discovery of this mutation has profoundly modified the diagnosis of Ph- MyeloProliferative Disorders (MPD), but its clinical significance still remains undefined.Using different technologies, characterized by various sensitivity and sensibility, it has been reported that the incidence of this mutation is ranging from 65% to 97% in PV, 25 to 57% in ET and 35 to 57% in CIMF. Those variations are mainly due to the heterogeneity and to the poor sensitivity of the assay used, highlighting the needs of a standardized, accurate and sensitive assay. The aim of this study was to validate the performances of a new allele specific RQPCR genotyping assay and to compare with the traditional PCR sequencing strategy.This assay benefit from the plasmid technology which allows the precise calibration and normalisation of RQ-PCR results and is highly reproducible. By generating standard curves based on the known concentration of plasmid dilutions, this technology allows precise measurement of the JAK2 wild type (WT) and V617F alleles copy number in human cell samples and, without the need of subsequent handling such as capillary electrophoresis or melting curve analysis, directly provides a normalized value which is independent of the cell count in each assayed sample. Normalized results can be compared between RQ-PCR systems and testing sites.For accuracy testing and determination of detection limit we used serial dilutions of V617F homozygous HEL cell line and genomic DNA mix into non mutated K562 cell or genomic DNA. Our data show a reproducible baseline threshold of 512 V617F homozygous cells in 5 10-6 WT cells (10-4) and 6.4 pg of positive genomic DNA (2.5 10-4, 48 copies) with very good correlations toward serial dilution in each case (R² = 0.99).The greater sensitivity of this assay allowed identifying 17% more mutated patients as compared with PCR sequencing. Healthy subjects and secondary polyglobuly patient samples always resulted WT (>99.9%). In patient samples VF allele range from 5 to 96% in positive cases and is always inferior to 0.3% in negative. No significant differences were observed in JAK2 V617F % range between the different diagnostic groups, but our results show differences in median value ranging from 80% for PV to 25% for ET and IMF. Results obtained on shared samples (n=32) in two different labs show a very high correlation (R²=0.98).The sensitivity and the dynamic range of the JAK2 V617F assay are compatible with its use for highly precise and sensitive quantification at diagnosis and during MRD follow-up. Validation of an equivalent assay for the quantification of the mutation on RNA is ongoing.
Comparative Urinary and Gallbladder Carcinogenicity of &lt;italic&gt;N&lt;/italic&gt;-[4-(5-Nitro-2-Furyl)-2-Thiazolyl]Formamide and &lt;italic&gt;N&lt;/italic&gt;-[4-(5-Nitro-2-Furyl)-2-Thiazolyl]Acetamide in the Dog&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: E. Ertürk, S. A. Atassi, Osamu Yoshida, S. M. Cohen, J. M. Price, George T. Bryan
Journal: JNCI Journal of the National Cancer Institute (1970)

N-[4-(5-nitro2-furyl)-2-thiazolyl]formamicle, a urinary bladder carcinogen for the rat and mouse, was fed to 4 female mongrel dogs at a dosage of about 50 mg/kg/day for 2 years followed by 9 months of normal diet. The incidences of tumors observed were: urinary bladder transitional cell carcinoma—4/4; ureteral transitional cell carcinoma—2/4; renal pelvis transitional cell carcinoma—2/4; gallbladder adenocarcinoma—4/4; mammary scirrhous carcinoma—2/4; and mammary fibroadenoma—2/4. A close structural analogue N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide, a carcinogen for the breast, salivary gland, lung, and kidney pelvis of the rat and a potent murine leukemogen, was fed to 2 other female mongrel dogs at the same dosage as N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide but for 30 months. The incidences of tumors observed were: gallbladder adenoma—-2/2 and mammary fibroadenoma—2/2. The seemingly minor structural difference of the two compounds significantly altered the distribution and degree of severity of the tumors. No tumors were found in one mongrel female maintained as a negative control.
Mammary Carcinogenic Effect of Low-Dose Fission Radiation in Wistar/Furth Rats and Its Dependency on Prolactin2
Authors: Kenjiro Yokoro, Chiyo Sumi, Akihiro Ito, Katsutomo Hamada, Keiji Kanda, Tooru Kobayashi
Journal: JNCI Journal of the National Cancer Institute (1980)

The mammary carcinogenic effect in rats of low-dose fission radiation and its dependency on prolactin were studied. A total of 141 female W/Fu rats were exposed to 4.8, 8.9, or 19.5 rads of fission radiation that had both fision neutrons of 2.0 million electron volts (MeV) and gamma ray components similar to those produced by the Hiroshima bomb. Only 1 of 48 rats (2.0%) developed mammary tumor (MT) after irradiation alone, whereas 20 of 48 rats (41.6%) developed MT's if prolactin was supplied shortly after irradiation by means of grafting of the prolactin-secreting pituitary tumor. Furthermore, MT's occurred in 11 of 45 rats (24.4%) treated with prolactin as late as 12 months after irradiation, which suggested the long-term survival of radiation-induced dormant MT cells. A correlation was found between the development of MT and the elevation of serum prolactin level; most MT's appeared shortly after the grafted mammotropic pituitary tumor became palpable. The growth of MT's appeared to be promoted by prolactin in collaboration with ovarian hormones; the growth of adenocarcinomas was dependent on prolactin and ovarian hormones, whereas the growth of fibroadenomas appeared to be less hormone-dependent. Much higher biologic effectiveness, especially in the low-dose range, was found with 2.0-MeV fission neutrons compared with 14.1-MeV fast neutrons or 180-kilovolt peak X-rays in rat mammary carcinogenesis.
Endovascular Stroke Treatment Outcomes After Patient Selection Based on Magnetic Resonance Imaging and Clinical Criteria
Authors: Thabele M. Leslie-Mazwi, Joshua A. Hirsch, Guido J. Falcone, Pamela W. Schaefer, Michael H. Lev, James D. Rabinov, Natalia S. Rost, Lee Schwamm, R. Gilberto González
Journal: JAMA Neurology (2015)

Which imaging modality is optimal to select patients for endovascular stroke treatment remains unclear.To evaluate the effectiveness of specific magnetic resonance imaging (MRI) and clinical criteria in the selection of patients with acute ischemic stroke for thrombectomy.In this observational, single-center, prospective cohort study, we studied 72 patients with middle cerebral artery or terminal internal carotid artery occlusion using computed tomographic angiography, followed by core infarct volume determination by diffusion weighted MRI, who underwent thrombectomy after meeting institutional criteria from January 1, 2012, through December 31, 2014. In this period, 31 patients with similar ischemic strokes underwent endovascular treatment without MRI and are categorized as computed tomography only and considered in a secondary analysis.Patients were prospectively classified as likely to benefit (LTB) or uncertain to benefit (UTB) using diffusion-weighted imaging lesion volume and clinical criteria (age, National Institutes of Health Stroke Scale score, time from onset, baseline modified Rankin Scale [mRS] score, life expectancy).The 90-day mRS score, with favorable defined as a 90-day mRS score of 2 or less.Forty patients were prospectively classified as LTB and 32 as UTB. Reperfusion (71 of 103 patients) and prospective categorization as LTB (40 of 103 patients) were associated with favorable outcomes (P < .001 and P < .005, respectively). Successful reperfusion positively affected the distribution of mRS scores of the LTB cohort (P < .001). Reperfusion was achieved in 27 LTB patients (67.5%) and 24 UTB patients (75.0%) (P = .86). Favorable outcomes were obtained in 21 (52.5%) and 8 (25.0%) of LTB and UTB patients who were treated, respectively (P = .02). Favorable outcomes were observed in 20 of the 27 LTB patients (74.1%) who had successful reperfusion compared with 8 of the 24 UTB patients (33.3%) who had successful reperfusion (P = .004). The ratio of treated to screened patients was 1:3.Prospective classification as LTB by MRI and clinical criteria is associated with likelihood of favorable outcome after thrombectomy, particularly if reperfusion is successful. Selection of patients using MRI compares favorably with selection using computed tomographic techniques with the distinction that a higher proportion of screened patients were treated.
PiSZ alpha-1 antitrypsin deficiency (AATD): pulmonary phenotype and prognosis relative to PiZZ AATD and PiMM COPD
Authors: C E Green, S Vayalapra, J A Hampson, D Mukherjee, R A Stockley, A M Turner
Journal: Thorax (2015)

The PiSZ genotype results in less severe deficiency of alpha-1 antitrypsin (AAT) than PiZZ. Less is known about phenotypic and prognostic features.We studied 699 PiZZ, 126 PiSZ and 316 PiMM patients. All AAT deficiency (AATD) patients were augmentation naive. PiSZ were compared with PiZZ patients for clinical phenotype at baseline including CT findings, smoke exposure, progression of lung disease and survival. Similarly, PiSZ patients diagnosed as a result of investigation for possible lung disease (lung index cases) were compared with PiMM. Multivariable analytical techniques and matching (PiSZ to PiZZ) were employed to account for demographic differences.Pack-years smoked and FEV1 exhibited a negative correlation in PiSZ and ZZ patients (both r=-0.43), with emphysema and COPD occurring more commonly in PiZZ patients at <20 pack-year exposure. In multivariable analyses, PiSZ patients were less likely to have emphysema (p<0.01) and had better survival than PiZZ (p=0.017), but lung function decline did not differ significantly. 42% of PiSZ patients had upper-zone-dominant emphysema on CT scan. Analyses of AAT level confirmed a critical threshold at 11 μM, particularly with regard to phenotypes classical of PiZZ AATD.Significant baseline differences suggested that PiSZ had presented earlier to health services than PiMM. Once this was accounted for, risk of emphysema did not differ between PiSZ and PiMM although survival was lower in PiMM patients (p<0.01).PiSZ patients are less susceptible to cigarette smoke than PiZZ. The pattern of emphysema may be similar at diagnosis to usual COPD.
Metal toxicity and the respiratory tract
Authors: B Nemery
Journal: European Respiratory Journal (1990)

The type of lung disease caused by metal compounds depends on the nature of the offending agent, its physicochemical form, the dose, exposure conditions and host factors. The fumes or gaseous forms of several metals, e.g. cadmium (Cd), manganese (Mn), mercury (Hg), nickel carbonyl (Nl(CO)4, zinc chloride (ZnCl2), vanadium pentoxide (V2O5), may lead to acute chemical pneumonitis and pulmonary oedema or to acute tracheobronchitis. Metal fume fever, which may follow the inhalation of metal fumes e.g. zinc (Zn), copper (Cu) and many others, is a poorly understood influenza-like reaction, accompanied by an acute self-limiting neutrophil alveolitis. Chronic obstructive lung disease may result from occupational exposure to mineral dusts, including probably some metallic dusts, or from jobs involving the working of metal compounds, such as welding. Exposure to cadmium may lead to emphysema. Bronchial asthma may be caused by complex platinum salts, nickel, chromium or cobalt, presumably on the basis of allergic sensitization. The cause of asthma in aluminium workers is unknown. It is remarkable that asthma induced by nickel (Ni) or chromium (Cr) is apparently infrequent, considering their potency and frequent involvement as dermal sensitizers. Metallic dusts deposited in the lung may give rise to pulmonary fibrosis and functional impairment, depending on the fibrogenic potential of the agent and on poorly understood host factors. Inhalation of iron compounds causes siderosis, a pneumoconiosis with little or no fibrosis. Hard metal lung disease is a fibrosis characterized by desquamative and giant cell interstitial pneumonitis and is probably caused by cobalt, since a similar disease has been observed in workers exposed to cobalt in the absence of tungsten carbide. Chronic beryllium disease is a fibrosis with sarcoid-like epitheloid granulomas and is presumably due to a cell-mediated immune response to beryllium. Such a mechanism may be responsible for the pulmonary fibrosis occasionally found in subjects exposed to other metals e.g. aluminium (Al), titanium (Ti), rare earths. The proportion of lung cancer attributable to occupation is around 15%, with exposure to metals being frequently incriminated. Underground mining of e.g. uranium or iron is associated with a high incidence of lung cancer, as a result of exposure to radon. At least some forms of arsenic, chromium and nickel are well established lung carcinogens in humans. There is also evidence for increased lung cancer mortality in cadmium workers and in iron or steel workers.